Preventives for hiv infection

ABSTRACT

It is intended to provide a novel drug which exhibits an excellent effect of preventing HIV infection in transfusing blood and using a blood preparation. This object can be achieved by a preventive for HIV infection in transfusing blood and using a blood prepartion characterized by containing a compound having an antagonism to a CC chemokine receptor (preferably antagonism to CCR5 and/or CCR2).

TECHNICAL FIELD

This invention relates to a medicine preventing HIV infection duringblood transfusion or when blood products are used, which contains acompound with a CC chemokine receptor (hereafter referred to as CCR)antagonistic effect.

BACKGROUND ART

HIV-1 uses CCR5 and/or CXCR4, which are one type of G-protein coupledreceptors (GPCR), as coreceptors during infection with CD4 positive Tcells (for example, see non-patent document 1, non-patent document 2,non-patent document 3, non-patent document 4, non-patent document 5, andnon-patent document 6). It has been found that GPCRs other than CCR5 andCXCR4, such as CCR2 (for example, see non-patent document 7), CCR3 (forexample, see non-patent document 5), APJ (for example, see non-patentdocument 8), Chem R23 (for example see non-patent document 9), GPR1,GPR15/BOB (for example, see non-patent document 10), and STRL33/BONZO(for example, see non-patent document 11) are also able to be used as acoreceptor However, the relationship of coreceptors other than CCR5 andCXCR4 to an actual HIV infection is uncertain. HIV-1 is referred to bydifferent names depending on the coreceptor used for it. The HIV-1 whichuses CCR5 as a coreceptor is referred to as R5 HIV-1, the HIV-1 whichuses CXCR4 as a coreceptor is referred to as X4 HIV-1, and the HIV-1which uses both of them is referred to as R5X4 HIV-1 (for example, seenon-patent document 12).

It is known that the ability of HIV-1 to use a coreceptor is closelyrelated to the condition of the HIV infection. That is, the firstinfection of HIV is caused by R5 HIV-1, R5 HIV-1 is primarily isolatedduring the symptomless period before the appearance of AIDS, and R5X4HIV-1 and X4 HIV-1 gradually come to be significantly isolated as theAIDS period approaches (for example, see non-patent document 13,non-patent document 14, and non-patent document 15).

It has been reported that the number of HIV positive samples in HIVscreening tests of blood donors in Japan in 2000 was 67 samples out ofabout 5.9 million blood donors. Amongst these positive samples, threesamples were negative in the antibody test and positive in the gene testand thus in the initial stages of infection, and it is thought thatthese blood donations were made during the so-called window period (theperiod from infection with HIV to the time when antibodies arepositively detected) (for example, see non-patent document 16). Inaddition, examples of infection in which infection due to bloodtransfusion cannot be denied have been reported from the antibodyscreening inspection has begun up until the present. These cases arethought to have been caused by transfusion during the window period (forexample, see non-patent document 17). Although the 22-day window periodwith the antibody test was shortened to 11 days due to the introductionof the gene test, infections caused by transfusion cannot be entirelyprevented by testing alone since there is still an 11-day window period.There are concerns about the increasing possibility of infections causedby transfusion during the window period in the future. In addition, forthe same reason, it cannot be denied that blood products such asimported standard management serums and immunoglobulin preparationswhich are produced from plasma and serums pooled from many people mayalso become infection sources in the future.

HIV infection during transfusion and when blood products are used iscaused by the fact that virus directly invades the blood and infects theCD4 positive lymphocytes. However in this case, the virus uses a CCRsuch as CCR5 as a coreceptor Therefore, it is thought that a compoundthat can obstruct binding of viruses to coreceptors and the invasion ofthe virus to the host cells, for example, a compound having a CCRantagonistic effect, can prevent HIV infection during blood transfusionand when blood products are used. Existing medicines such as reversetranscriptase inhibitors and protease inhibitors cannot be expected tobe useful for the prevention of infection since these act after thevirus has invaded the host cells. Up until now, the present inventorshave reported that TAK-779 having a. CCR5 antagonistic effect exhibitsan inhibitory effect against HIV-1 infection caused by R5 HIV-1 (forexample, see non-patent document 18). In addition, polymorphism in thegenes of the chemokine receptors of Japanese hemophiliacs that have hadno occurrence of disease over a long period of time and were negative inHIV antibody test have been examined. It has been reported that a genepolymorphism in CCR2-64I/CCR5-59653T in such high risk factor groups notonly takes part in the obstruction of the occurrence of AIDS but alsotakes part in the obstruction of HIV infection (for example, seenon-patent document 19). It is suggested that CCR5 and/or CCR2 plays animportant role in the establishment of HIV infection.

Meanwhile, various compounds having a CCR antagonistic effect are known(for example, see patent documents 1-9). However, a compound having aCCR antagonistic effect that prevent HIV infection during bloodtransfusion and when blood products are used has not been reported.

Prior art documents relating to the invention of the present applicationare as follows.

Non-Patent Document 1

-   -   Science 272, 872-877 (1996)        Non-Patent Document 2:    -   Nature 381, 661-666 (1996)        Non-Patent Document 3:    -   Nature 381, 667-673 (1996)        Non-Patent Document 4:    -   Science 272, 1955-1958 (1996)        Non-Patent Document 5:    -   Cell 85, 1135-1148 (1996)        Non-Patent Document 6:    -   Cell 85, 1149-1158 (1996)        Non-Patent Document 7:    -   Cell 87, 437-446 (1996)        Non-Patent Document 8:    -   J. Virol. 72, 6113-6118 (1998)        Non-Patent Document 9:    -   Eur. J. Immunol. 28, 1689-1700 (1998)        Non-Patent Document 10:    -   J. Exp. Med. 186, 405-411 (1997)        Non-Patent Document 11:    -   J. Exp. Med. 185, 2015-2023 (1997)        Non-Patent Document 12:    -   Nature 391, 240 (1998)        Non-Patent Document 13:    -   J. Virol. 66, 1354-1360 (1992)        Non-Patent Document 14:    -   J. Infect. Dis. 169, 968-974 (1994)        Non-Patent Document 15:    -   J. Exp. Med. 185, 621-628 (1997)        Non-Patent Document 16:    -   Sogo Rinsho 50, 2698-2703 (2001)        Non-Patent Document 17:    -   Mebio 15, 6-11 (1999)        Non-Patent Document 18:    -   Proc. Natl. Acad. Sci. USA, 96, 5698-5703(1999)        Non-Patent Document 19:    -   The 15th Annual Congress of the Japanese Society for AIDS        Research (December, 2001)        Patent Publication 1:    -   WO 99/32468        Patent Publication 2:    -   WO 99/32100        Patent Publication 3:    -   WO 00/10965        Patent Publication 4:    -   WO 00/37455        Patent Publication 5:    -   WO 00/68203        Patent Publication 6:    -   WO 00/76993        Patent Publication 7:    -   WO 00/66551        Patent Publication 8:    -   WO 01/25200        Patent Publication 9:    -   WO 01/25199

OBJECTS OF THE INVENTION

The present invention provides a new medicine that specificallydemonstrates a remarkable effect in the prevention of HIV infectionduring blood transfusion and when blood products are used.

SUMMARY OF THE INVENTION

There is a possibility that HIV that contaminates blood that is donatedor shared in the window period will not detected by screening tests. Asa result, there is a possibility that HIV will infect the recipientduring blood transfusion or when blood products are used. Thus, thepresent inventors focused on the possibility that a medicine having aCCR antagonistic effect would be able to work as an HIV infectionpreventative, and as a result of extensive studies, found that amedicine having a CCR5 antagonistic effect is useful for the preventionof HIV infection, and completed the present invention.

That is, the present invention relates to:

-   -   (1) An agent for preventing HIV infection in transfuing blood or        using a blood product (blood preparation), which comprises a        compound having a CCR antagonistic effect;    -   (2) An agent as shown in the above (1), wherein CCR is CCR5        and/or CCR2;    -   (3) An agent as shown in the above (1), wherein the compound        having a CCR antagonistic effect is        N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-N-{3-[4-({4-[(methylsulfonyl)amino]phenyl}sulfonyl)-1-piperidinyl]propyl}-4-piperidinecarboxamide,        N-(3-chlorophenyl)-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamide,        N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        1-acetyl-N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3-chloro-4-methylphenyl)-4-piperidinecarboxamide,        N-(3,4-dichlorophenyl)-N-(3-{4-[4-(ethylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        N-(3,4-dichlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        N-(3-chlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        N-(3-chlorophenyl)-N-(3-{4-[4-(ethylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamide,        N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3-chloro-4-methylphenyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,        N-[3-(4-benzyl-1-piperidinyl)propyl]-N′-(4-chlorophenyl)-N-phenylurea,        N′-(4-chlorophenyl)-N-{3-[4-(4-fluorobenzyl)-1-piperidinyl]propyl}-N-phenylurea,        N′-(4-chlorophenyl)-N-(3-{4-[4-(4-morpholinylsulfonyl)benzyl]-1-piperidinyl}propyl)-N-phenylurea,        N′-(4-chlorophenyl)-N-(3-{4-[4-(4-methylsulfonyl)benzyl]-1-piperidinyl}propyl)-N-phenylurea,        4-{[1-(3-{[(4-chloroanilino)carbonyl]anilino}propyl)-4-piperidinyl]methyl}benzamide,        N-[3-(4-benzyl-1-piperidinyl)propyl]-N-(3,4-dichlorophenyl)-1-methyl-5-oxo-3-pyrrolidinecarboxamide,        1-benzyl-N-[3-(4-benzyl-1-piperidinyl)propyl]-5-oxo-N-phenyl-3-pyrrolidinecarboxamide,        N-[3-(4-benzyl-1-piperidinyl)propyl]-1-(2-chlorobenzyl)-5-oxo-N-phenyl-3-pyrrolidinecarboxamide,        N-(3,4-dichlorophenyl)-N-{3-[4-(4-fluorobenzyl)-1-piperidinyl]propyl}-1-methyl-5-oxo-3-pyrrolidinecarboxamide        and        N-[3-(4-benzyl-1-piperidinyl)propyl]-5-oxo-N-phenyl-1-(2,2,2-trifluoroethyl)-3-pyrrolidinecarboxamide,        N-(3,4-dichlorophenyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-2-[1-(methylsulfonyl)-4-piperidinyl]acetamide,        N-(3,4-dichlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-2-[1-(methylsulfonyl)-4-piperidinyl]acetamide,        3-(1-acetyl-4-piperidinyl)-N-(3,4-dichlorophenyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)propanamide,        N-(3,4-dichlorophenyl)-4-hydroxy-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamide        or a salt thereof;    -   (4) A preventing agent as shown in the above (1), wherein the        compound having a CCR antagonistic effect is        N-methyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]piperidinium        iodide,        N-methyl-N-[4-[[[7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-yl]carbonyl]amino]benzyl]piperidinium        iodide,        N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-carboxamide,        N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1-benzoxepin-4-carboxamide,        7-(4-ethoxyphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-2,3-dihydro-1-benzoxepin-4-carboxamide,        N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]-N-(tetrahydropyran-4-yl)ammonium        iodide,        N-methyl-N-[4-[[[7-(4-methylphenyl)-3,4-dihydronaphthalen-2-yl]carbonyl]amino]benzyl]piperidinium        iodide,        N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)ammonium        chloride,        N,N-dimethyl-N-(((7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-yl)        carbonyl)amino)benzyl)-N-(4-oxocyclohexyl)ammonium chloride,        N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammonium        chloride,        N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-propoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-(4-butoxyphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[4-[N-methyl-N-(2-propoxyethyl)amino]phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[4-(2-ethoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[4-(2-ethoxyethoxy)-3,5-dimethylphenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[2-chloro-4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-(3-methyl-4-propoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-(3,4-dipropoxyphenyl)-N-(4-((N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,        7-[4-(2-ethoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        1-ethyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-ethoxyethoxy)phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        1-formyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-1-propyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-1-propyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        1-benzyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-phenyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-(3,4-methylenedioxy)phenyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-(2-methyloxazol-5-yl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        1-allyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(3-thienyl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(thiazol-2-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-(1-methylpyrazol-4-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-(3-methylisothiazol-5-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-(1-ethylpyrazol-4-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        1-isobutyl-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(thiazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(1-methyltetrazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,        or        7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(2-methyltetrazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide        or a salt thereof;    -   (5) Blood for transfusion or blood product, which contains a        compound having a CCR antagonistic effect;    -   (6) A method for preventing HIV infection, which comprises        administering blood for transfusion or a blood product which        contains a compound having a CCR antagonistic effect;    -   (7) A method for preventing HIV infection, which comprises        administering an effective amount of a compound having a CCR        antagonistic effect at the time of blood transfusion or blood        product use;    -   (8) A method as shown in the above (7), wherein the time of        blood transfusion or blood product use is from one hour before        blood transfusion or blood product use to the time of blood        transfusion or blood product use; and the like.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a graph showing the HIV-1 infection inhibition rate of acompound used in the experimental examples.

DETAILED DESCRIPTION OF THE INVENTION

Among the compounds having a CCR antagonistic effect used in the presentinvention, compounds having a CCR5 and/or a CCR2 antagonistic effect areparticularly preferred, especially the compounds having a CCR5antagonistic effect. That is, compounds having an antagonistic effect onone receptor from amongst the CCR5 and CCR2 receptors or both thereceptors are preferable.

For example, anilide compounds shown in WO99/32468, WO99/32100 andWO00/68203 are mentioned as the compounds having CCR2 antagonisticeffect. For example, piperidine derivatives (WO00/66551, WO01/25199,WO01/25200, Japanese patent application No. 2000-328851) and anilidederivatives having a quarternal ammonium moiety (for example, compoundsshown in non-patent document 18 mentioned above and compounds shown inJ. Med. Chem. 2000, 43, 2049-2063) other than the above anilidecompounds are mentioned as the compound having a CCR5 antagonisticeffect.

More specifically, the following compounds are mentioned.

(1) a compound having a CCR5 antagonistic effect which is represented bythe formula:

(wherein R^(a1) is a hydrogen atom, a hydrocarbon group which maybesubstituted, a non-aromatic heterocyclic group which may be substituted,R^(a2) is a hydrocarbon group which may be substituted, a non-aromaticheterocyclic group which may be substituted, or R^(a1) and R^(a2) maycombine to each other together with A^(a), to form a heterocyclic groupwhich may be substituted; A^(a) is N or N⁺—R^(a5).Y^(a−) (R^(a5) is ahydrocarbon group; Y^(a−) is a counter anion); R^(a3) is a cyclichydrocarbon group which may be substituted or a heterocyclic group whichmay be substituted; na is 0 or 1; R^(a4) is a hydrogen atom, ahydrocarbon group which may be substituted, a heterocyclic group whichmay be substituted, an alkoxy group which may be substituted, an aryloxygroup which may be substituted, or an amino group which may besubstituted, E^(a) is a divalent aliphatic hydrocarbon group which maybe substituted by a group other than an oxo group; G^(a1) is a bond, COor SO₂; G^(a2) is CO, SO₂, NHCO, CONH or OCO; J^(a) is methine or anitrogen atom; and each of Q^(a) and R^(a) is a bond or a divalent C₁₋₃aliphatic hydrocarbon which may be substituted; provided that J^(a) ismethine when G^(a2) is OCO, that one of Q^(a) and R^(a) is not a bondwhen the other is a bond and that each of Q^(a) and R^(a) is notsubstituted by an oxo group when G^(a1) is a bond) or a salt thereof.

(2) a compound of the formula:

-   [wherein R^(b1) is a hydrocarbon group which may be substituted;-   R^(b2) is a cyclic hydrocarbon group which may be substituted or a    heterocyclic group which may be substituted;-   R^(b3) is a halogen atom, a carbamoyl group which may be    substituted, a sulfamoyl group which may be substituted, an acyl    group derived from a sulfonic acid, a C₁₋₄ alkyl group which may be    substituted, a C₁₋₄ alkoxy group which may be substituted, an amino    group which may be substituted, a nitro group or a cyano group;-   R^(b4) is a hydrogen atom or a hydroxy group;-   nb is an integer of 0 or 1;-   pb is an integer of 0 or 1 to 4];    or a salt thereof,

(3) a compound of the formula:

wherein R^(c1) is a hydrocarbon group, R^(c2) is a hydrocarbon grouphaving 2 or more carbon atoms, or R^(c1) and R^(c2) may join to form,together with an adjacent nitrogen atom, a ring optionally having asubstituent or substituents, R^(c3) is a hydrocarbon group optionallyhaving a substituent or substituents or a heterocyclic group optionallyhaving a substituent or substituents, R^(c4) is a hydrogen atom, ahydrocarbon group optionally having a substituent or substituents or aheterocyclic group optionally having a substituent or substituents,E^(c) is a divalent chain hydrocarbon group optionally having asubstituent or substituents other than an oxo group, G^(c) is CO or SO₂,J^(c) is a nitrogen atom or a methine group optionally having asubstituent or substituents, and Q^(c) and R^(c) are each a bond or adivalent chain C₁₋₃ hydrocarbon group optionally having a substituent orsubstituents, or a salt thereof;

(4) a compound of the formula:

wherein A^(d) is a group represented by the formula:

wherein R^(d3) is (1) a hydrocarbon group which may be substituted, (2)a C₁₋₄ alkoxy group which may be substituted or (3) an amino group whichmay be substituted; X^(d) is a bond, —SO₂— or —CO—; nd is an integer of1 to 3; md is 0 or an integer of 1 to 3; R^(d4) and R^(d5) are the sameor different and each of which is a hydrogen atom or a C₁₋₆ alkyl group;R^(d6) is a hydroxyl group, a C₁₋₆ alkyl group or a C₂₋₆ alkenyl group;rd is an integer of 2 to 4; B^(d) is a bond, —CH₂—, —SO₂—, —SO—, —S—,—O—, —CO—, —N^(da)—SO₂— or —NR^(da)—CO— (wherein R^(da) is a hydrogenatom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group or a C₃₋₈ cycloalkylgroup); each of pd and qd is 0 or an integer of 1 to 4; R^(d1) is ahalogen atom, a C₁₋₆ alkyl group, a C₂₋ alkenyl group, a C₁₋₄ alkanoylgroup, a C₁₋₄ alkoxy group, a cyano group, a trifloromethyl group, anitro group, a hydroxyl group, an amino group or an amidino group;R^(d2) is 1) a halogen, 2) a C₁₋₆ alkyl which may be substituted by ahalogen or a C₁₋₄ alkoxy, 3) a C₁₋₄ alkoxy which may be substituted by ahalogen or a C₁₋₄ alkoxy, 4) nitro, 5) cyano, 6) hydroxyl, 7) a C₁₋₄alkanoylamino, 8) SO₂NR^(db)R^(dc), 9) SO₂R^(dd), 10) CONR^(db)R^(dc),11) NR^(db)R^(dc) or 12) NR^(da)—SO₂R^(dd) {wherein R^(da) has themeaning given above, and R^(db) and R^(dc) may be the same or different,and each of which (1) a hydrogen, (2) a C₁₋₆ alkyl group which may besubstituted by a halogen or a C₁₋₄ alkoxy or (3) a C₃₋₈ cycloalkyl groupwhich may be substituted by a halogen or a C₁₋₄ alkoxy, or R^(db) andR^(dc) may, taken together with nitrogen atom form a cyclic amino group;R^(dd) is a C₁₋₆ alkyl group or a C₃₋₈ cycloalkyl group} each R^(d1),may be the same or different from each other when pd is two or more, andeach R^(d2), may be the same or different from each other when qd is twoor more; or a salt thereof.

(5) a compound represented by formula:R^(e1)—X^(e1)—W^(e)—X^(e2)-Z^(e1)-Z^(e2)-R^(e2)  (el)[wherein R^(e1) represents a 5 to 6-membered cyclic ring group which maybe substituted, X^(e1) represents a bond or a bivalent group, in whichthe number of atoms constituting the straight-chain portion is 1 to 4,W^(e) represents a bivalent group represented by formula:

(wherein each of ring A^(e) and ring B^(e) represents a 5- to 7-memberedring group which may be substituted, each of Ee₁ and Ee₄ is the carbonatom which may be substituted or a nitrogen atom which may besubstituted, each of Ee₂ and Ee₃ is the carbon atom which may besubstituted, the nitrogen atom which may be substituted, a sulfur whichmay be oxidized or an oxygen atom and each of a^(e) and b^(e) is asingle bond or a double bond), X^(e2) is a bivalent group, in which thenumber of atoms constituting the straight-chain portion is 1 to 4,Z^(e1) is a bond or a bivalent cyclic ring group, Z^(e2) is a bond or abivalent cyclic ring group, in which the number of atoms constitutingthe straight-chain portion is 1 to 4, and R^(e2) is (1) an amino groupwhich may be substituted, where the nitrogen atom may be converted intoa quaternary ammonium or the N-oxide, (2) a nitrogen-containingheterocyclic ring group which may be substituted and may contain sulfuratom or an oxygen atom as a ring-constituting atom, where the nitrogenatom may be converted into a quaternary ammonium or a N-oxide, (3) agroup which is bonded via the sulfur atom, (4) a group represented byformula

(wherein ek is 0 or 1, the phosphorus atom may form a phosphonium saltwhen k is 0, and each of R^(e5′) and R^(e6′) is a hydrocarbon atom whichmay be substituted, a hydroxyl group which may be substituted or anamino group which may be substituted and R^(e5′) and R^(e6′) may bindeach other to form a cyclic ring group together with the adjacentphosphorus atom), (5) an amidino group which may be substituted or (6) aguanidino group which may be substituted].

As the compound of the above formula (eI) or a salt thereof, thefollowing compounds are mentioned.

1) a compound of the formula:

wherein R^(e1) is an optionally substituted 5- to 6-membered ring,W^(ea) is a divalent group represented by the formula:

wherein the ring A^(ea) is an optionally substituted 5- to 6-memberedaromatic ring, X^(ea) is an optionally substituted carbon atom, anoptionally substituted nitrogen atom, a sulfur atom or an oxygen atom,the ring B^(e) is an optionally substituted 5- to 7-membered ring;Z^(e2) is a bond or a divalent group in which the number of carbon atomsconstituting the straight-chain portion is 1 to 4, R^(e2a) is (1) anoptionally substituted amino group in which a nitrogen atom may form aquaternary ammonium, (2) an optionally substituted nitrogen-containingheterocyclic ring group which may contain a sulfur atom or an oxygenatom as ring constituting atoms and wherein a nitrogen atom may form aquaternary ammonium, (3) a group binding through a sulfur atom or (4) agroup of the formula:

wherein ek is 0 or 1, and when ek is 0, a phosphorus atom may form aphosphonium; and R^(e5) and R^(e6) are independently an optionallysubstituted hydrocarbon group or an optionally substituted amino group,and R^(e5) and R⁶ may bind to each other to form a cyclic group togetherwith the adjacent phosphorus atom, or a salt thereof,

2) a compound of the formula:

wherein R^(e1b) is an optionally substituted phenyl group or anoptionally substituted thienyl group; Y^(eb) is —CH₂—, —O— or —S—; andR^(e2b), R^(e3b) and R^(e4b) are independently an optionally substitutedaliphatic hydrocarbon group or an optionally substituted alicyclicheterocyclic ring group; or a salt thereof,

3) a compound of the formula:

wherein R^(e1) is an optionally substituted 5- to 6-membered ring; thering A^(ec) is an optionally substituted 6- to 7-membered ring; the ringB^(ec) is an optionally substituted benzene ring; n^(ec) is an integerof 1 or 2; Z^(e2) is a bond or a divalent group in which the number ofcarbon atoms constituting the straight-chain is 1 to 4; R^(e2c) is (1)an optionally substituted amino group in which a nitrogen atom may forma quaternary ammonium, (2) an optionally substituted nitrogen-containingheterocyclic ring group which may contain a sulfur atom or an oxygenatom as ring constituting atoms and wherein a nitrogen atom may form aquaternary ammonium, (3) a group binding through a sulfur atom or (4) agroup of the formula:

wherein ek is 0 or 1, and when ek is 0, a phosphorus atom may form aphosphonium; and R^(e5′) and R^(e6′) are independently an optionallysubstituted hydrocarbon group, an optionally substituted hydroxy groupor an optionally substituted amino group, and R^(e5′) and R^(e6′) maybind to each other to form a cyclic group together with the adjacentphosphorus atom, or a salt thereof;

4) a compound of the formula:

wherein R^(e1d) is a 5- to 6-membered aromatic ring which has a group ofthe formula: R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- wherein R^(ed) is a hydrogenatom or an optionally substituted hydrocarbon group, X^(ed) is anoptionally substituted alkylene chain, and Z^(e1d) and Z^(e2d) arerespectively hetero-atoms, and which may have a further substituent, thegroup R^(ed) may bind to the 5-6 membered aromatic ring to form a ring,Y^(ed) is an optionally substituted imino group, R^(e2d) and R^(e3d) arerespectively an optionally substituted aliphatic hydrocarbon group or anoptionally substituted alicyclic heterocyclic group; or a salt thereof.

In the formula (I), the “hydroxarbon group” in the “hydrocarbon groupwhich may be substituted” represented by R^(a1) includes e.g. analiphatic chain hydrocarbon group, an alicyclic hydrocarbon group and anaryl group, preferably, an aliphatic chain hydrocarbon group and analicyclic hydrocarbon group.

Examples of the “aliphatic hydrocarbon group” include e.g. astraight-chain or branched aliphatic hydrocarbon group such as an alkylgroup, an alkenyl group, an alkynyl group, etc., preferably an alkylgroup. Examples of the alkyl group include e.g. a C₁₋₁₀ alkyl group(preferably a C₁₋₆ alkyl, etc.) such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neopentyl, 1-methylpropyl, n-hexyl, isohexyl,1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl,3,3-dimethylpropyl, 2-ethylbutyl, n-heptyl, 1-methylheptyl,1-ethylhexyl, n-octyl, 1-methyl-heptyl, nonyl, etc. Examples of thealkenyl group include e.g. a C₂₋₆ alkenyl group such as vinyl, allyl,isopropenyl, 2-methyl-allyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl,2-butenyl, 3-butenyl, 2-ethyl-1-butenyl, 2-methyl-2-butenyl,3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,5-hexenyl, etc. Examples of the alkynyl group include e.g. a C₂₋₆alkynyl group such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl,2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl,1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, etc.

Examples of the “alicyclic hydrocarbon group” include e.g. a saturatedor unsaturated alicyclic hydrocarbon group such as a cycloalkyl group, acycloalkenyl group, a cycloalkanedienyl group, etc., preferablycycloalkyl group. Examples of the “cycloalkyl group” include e.g. a C₃₋₉cycloalkyl (preferably a C₃₋₈ cycloalkyl) such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclononyl, etc., and a fused ring such as 1-indanyl, 2-indanyl, etc.Examples of the “cycloalkenyl group” include e.g. a C₃₋₆ cycloalkenylgroup such as 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl,3-cyclohexen-1-yl, 1-cyclobuten-1-yl, 1-cyclopenten-1-yl, etc. Examplesof the “cycloalkanedienyl group” include e.g. a C₄₋₆ cycloalkanedienylgroup such as 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl,2,5-cyclohexadien-1-yl, etc.

Examples of the “aryl group” include e.g. a monocyclic or fusedpolycyclic aromatic hydrocarbon group. Among others, a C₆₋₁₄ aryl groupsuch as phenyl, naphthyl, anthryl, phenathryl, acenaphthylenyl,4-indanyl, 5-indanyl, etc. are preferable. In particular, phenyl,1-naphthyl, 2-naphthyl, etc. are preferable.

Examples of the “non-aromatic heterocyclic group” in the “optionallysubstituted non-aromatic heterocyclic group” represented by R^(a1)include a 3- to 8-membered (preferably 5- or 6-membered) saturated orunsaturated (preferably saturated) non-aromatic heterocyclic group(alicyclic heterocyclic group) such as oxiranyl, azetidinyl, oxetanyl,thiethanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl,tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.

Examples of the substituent of the “optionally substituted hydrocarbongroup” and “optionally substituted non-aromatic heterocyclic group”represented by R^(a1) include an optionally substituted alkyl group, anoptionally substituted alkenyl group, an optionally substituted alkynylgroup, an optionally substituted aryl group, an optionally substitutedcycloalkyl or cycloalkenyl group, an optionally substituted heterocyclicgroup, an optionally substituted amino group, an optionally substitutedimidoyl group, an optionally substituted amidino group, an optionallysubstituted hydroxyl group, an optionally substituted thiol group, anoptionally esterified carboxyl group, an optionally substitutedcarbamoyl group, an optionally substituted thiocarbamoyl group, anoptionally substituted sulfamoyl group, a halogen atom (e.g. fluorine,chlorine, bromine, iodine, etc., preferably chlorine, bromine, etc.), acyano group, a nitro group, an acyl group derived from a sulfonic acid,an acyl group derived from an carboxylic acid, an optionally substitutedalkyl-sulfinyl group, an optionally substituted aryl-sulfinyl group,etc. The “optionally substituted hydrocarbon group” and “optionallysubstituted non-aromatic heterocyclic group” may have 1 to 5substituents as described above (preferably 1 to 3 substituents) at anypossible position.

Examples of the aryl group in the “optionally substituted aryl group” asthe substituent include a C₆₋₁₄ aryl group such as phenyl, naphthyl,anthryl, phenathryl, acenaphthylenyl, etc. Examples of the substituentof the aryl group include a lower alkoxy group which may be substitutedby halogen (e.g. a C₁₋₆ alkoxy group such as methoxy, ethoxy, propoxy,etc., a C₁₋₄ alkoxy group substituted by halogen such as fluoromethoxy,difluoromethoxy, trifluoromethoxy, 1,1-difluoroethoxy,2,2-difluoroethoxy, 3,3-difluoropropoxy, 2,2,3,3,3-pentafluoropropoxy,etc.), an aryloxy which may be substituted (e.g., phenoxy,4-fluorophenoxy, 2-carbamoylphenoxy, etc.), a halogen atom (e.g.,fluorine, chlorine, bromine, iodine, etc.), a lower alkyl group whichmay be substituted (an unsubstituted C₁₋₆ alkyl group such as methyl,ethyl, propyl, etc., a C₁₋₄ alkyl group substituted by halogen such asfluoromethyl, difluoromethyl, trifluoromethyl, 1,1-difluoroethyl,2,2-difluoroethyl, 3,3-difluoropropyl, 2,2,3,3,3-pentafluoropropyl,etc.), a C₃₋₈ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, etc.), an amino group, a mono-substituted amino(e.g., carbamoylamino, methylsulfonylamino, methylamino, ethylamino,propylamino, etc.), di-substituted amino (e.g., dimethylamino,diethylamino, N-methyl-N-methylsulfonylamino, di(methylsulfonyl)amino,etc.), a carbamoyl group which may be substituted by a C₁₋₆ alkyl (e.g.,butylcarbamoyl, etc.), formyl, a C₂₋₆ alkanoyl group (e.g., a C₂₋₆alkanoyl such as acetyl, propionyl, butyryl, etc.), a C₆₋₁₄ aryl group(e.g., phenyl, naphthyl, etc.), a C₆₋₁₄ aryl carbonyl (e.g., benzoyl,naphthoyl, etc.), a C₇₋₁₃ aralkyl carbonyl (e.g., benzylcarbonyl,naphthylmethylcarbonyl, etc.), a hydroxyl group, an alkanoyloxy (a C₂₋₅alkanoyloxy such as acetyloxy, propionyloxy, butyryloxy, etc.), a C₇₋₁₃aralkyl-carbonyloxy (e.g., benzylcarbonyloxy, etc.), a nitro group, asulfamoyl group which may be substituted (e.g., unsubstituted sulfamoylgroup, N-methylsulfamoyl, etc.), an arylthio group which may besubstituted (e.g., phenylthio, 4-methylphenylthio, etc.), —N═N-phenyl, acyano group, an amidino group, a carboxyl group which may be esterified(free carboxyl group, and a C₁₋₄ alkoxy carbonyl such asmethoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, etc., etc.), a C₁₋₆alkylthio, a C₁₋₆ alkylsulfinyl, a C₁₋₆ alkylsulfonyl, a C₆₋₁₄ arylthio,a C₆₋₁₄ arylsulfinyl, a C₆₋₁₄ arylsulfonyl, a heterocyclic group whichmay be substituted (e.g., pyridyl, thienyl, tetrazolyl, morpholinyl,oxazolyl, etc. and those as mentioned below for the definition ofheterocyclic group which may be substituted shown as R^(a3)), etc. Oneor two of these substituents may be present at any substitutableposition.

Examples of the cycloalkyl group in the “optionally substitutedcycloalkyl group” as the substituent include e.g. a C₃₋₇ cycloalkylgroup such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, etc. Examples of the substitutent of said cycloalkyl groupsmay have the same number and kind of substituents as those of the abovedescribed “optionally substituted aryl group”.

Examples of the cycloalkenyl group in the “optionally substitutedcycloalkenyl group” as the substituent include e.g. a C₃₋₆ cycloalkenylgroup such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl,etc. Example of the substitutent of the cycloalkenyl groups which may besubstituted may have the same number and kind of substituents as thoseof the above described “optionally substituted aryl group”.

Examples of the alkyl group in the “optionally substituted alkyl group”as the substituent include e.g. a C₁₋₆ alkyl etc. such as methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neopentyl, 1-methylpropyl, n-hexyl, isohexyl,1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl,3,3-dimethylpropyl, etc. Examples of the susbstitutent of said alkylgroups may have the same number and kind of substituents as those of theabove described “optionally substituted aryl group”.

Examples of the alkenyl group in the “optionally substituted alkenylgroup” as the substituent include e.g. a C₂₋₆ alkenyl group such asvinyl, allyl, isopropenyl, 2-methylallyl, 1-propenyl,2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-ethyl-1-butenyl,2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl,3-hexenyl, 4-hexenyl, 5-hexenyl, etc. Examples of the substitutents ofsaid alkenyl groups may have the same number and kind of substituents asthose of the above described “optionally substituted aryl group”.

Examples of the alkynyl group in the “optionally substituted alkynylgroup” as the substituent include e.g. a C₂₋₆ alkynyl group such asethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl,1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl,3-hexynyl, 4-hexynyl, 5-hexynyl, etc. Examples of the substituent ofsaid alkynyl groups may have the same kind and number of substituents asthose of the above described “optionally substituted aryl group”.

Examples of the heterocyclic group in the “optionally substitutedheterocyclic group” as the substituent include e.g. an aromaticheterocyclic group, saturated or unsaturated non-aromatic heterocyclicgroup (alicyclic heterocyclic group) etc., which contains at least onehetero-atom (preferably 1 to 4 hetero-atoms, more preferably 1 to 2hetero-atoms) consisting of 1 to 3 kinds of hetero-atoms (preferably 1to 2 kinds of hetero-atoms) selected from an oxygen atom, a sulfur atom,a nitrogen atom, etc.

Examples of the “aromatic heterocyclic group” include an aromaticmonocyclic heterocyclic group such as a 5- to 6-membered aromaticmonocyclic heterocyclic group (e.g. furyl, thienyl, pyrrolyl, oxazolyl,isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, etc.); an aromatic fused heterocyclicgroup such as a 8- to 12-membered aromatic fused heterocyclic group(e.g. benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl,1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzoisooxazolyl,benzothiazolyl, 1,2-benzoisothiazolyl, 1H-benzotriazolyl, quinolyl,isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl,naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl,β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl,phenazinyl, phenoxathinyl, thianthrenyl, phenanthridinyl,phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl,pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl,imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl,1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.);etc., preferably, a heterocyclic group consisting of the above-mentioned5- or 6-membered aromatic monocyclic heterocyclic group fused with abenzene ring or a heterocyclic group consisting of the above-mentioned5- or 6-membered aromatic monocyclic heterocyclic group fused with thesame or different above-mentioned 5- or 6-membered aromatic monocyclicheterocyclic group, etc.

Examples of the “non-aromatic heterocyclic group” include e.g. a 3- to8-membered (preferably 5- or 6-membered) saturated or unsaturated(preferably saturated) non-aromatic heterocyclic group (alicyclicheterocyclic group) such as oxiranyl, azetidinyl, oxetanyl, thiethanyl,pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl,tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.

Examples of the substituent of the “optionally substituted heterocyclicgroup” as the substituent include a lower alkyl group (e.g. a C₁₋₆ alkylgroup such as methyl, ethyl, propyl, etc.), an acyl group (e.g. a C₁₋₆alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., e.g. an arylcarbonyl such as benzoyl, etc., e.g. a C₁₋₆ alkylsulfonyl such asmethylsulfonyl, ethylsulfonyl, etc., e.g. a substituted sulfonyl such asaminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, etc.), alower alkyl substituted by a halogen (e.g., trifluoromethyl,1,1-difluoroethyl, etc.), etc.

Examples of the substituent in the “optionally substituted amino group”,“optionally substituted imidoyl group”, “optionally substituted amidinogroup”, “optionally substituted hydroxyl group” and “optionallysubstituted thiol group” as the substituent include e.g. a lower alkylgroup (e.g. a C₁₋₆ alkyl group such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), aryl group (e.g.,phenyl, 4-methylphenyl, etc.), acyl group (C₁₋₆ alkanoyl (e.g., formyl,acetyl, propionyl, pivaloyl, etc.), e.g. aryl-carbonyl (e.g. benzoyl,etc.), C₁₋₆ alkylsulfonyl (e.g., methylsulfonyl, ethylsulfonyl, etc.)C₆₋₁₄ aryl-sulfonyl (e.g., para-toluenesulfonyl, etc.), etc.,substituted-sulfonyl such as aminosulfonyl, methylaminosulfonyl,dimethylaminosulfonyl, etc.), an optionally halogenated C₁₋₆alkoxy-carbonyl (e.g. trifluoromethoxycarbonyl,2,2,2-trifluoroethoxycarbonyl, trichloromethoxycarbonyl,2,2,2-trichloroethoxycarbonyl, etc.), etc. In addition, the “aminogroup” in the “optionally substituted amino group” as the substituentmay be substituted with an optionally substituted imidoyl group (e.g., aC₁₋₆ alkylimidoyl, formimidoyl, amidino, etc.), etc. and twosubstituents of the “amino group” may form a cyclic amino group togetherwith a nitrogen atom. Examples of said cyclic amino group include e.g.3- to 8-membered (preferably 5- to 6-membered) cyclic amino group suchas 1-azetidinyl, 1-pyrrolidinyl, piperidinol-piperidinyl,morpholino4-morpholinyl, 1-piperazinyl and 1-piperazinyl which may haveat the 4-position a lower alkyl group (e.g. a C₁₋₆ alkyl group such asmethyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.),an aralkyl group (e.g. a C₇₋₁₀ aralkyl group such as benzyl, phenethyl,etc.), an aryl group (e.g. a C₆₋₁₀ aryl group such as phenyl,1-naphthyl, 2-naphthyl, etc.), etc.

Examples of the “optionally substituted carbamoyl group” includeunsubstituted carbamoylas well as a N-mono-substituted carbamoyl groupand a N,N-di-substituted carbamoyl group.

The “N-mono-substituted carbamoyl group” is a carbamoyl group having onesubstituent on the nitrogen atom and said substituent include e.g. alower alkyl group (e.g. a C₁₋₆ alkyl group such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), acycloalkyl group (e.g. a C₃₋₆ cycloalkyl group such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, etc.), an aryl group (e.g. a C₃₋₆aryl group such as phenyl, 1-naphthyl, 2-naphthyl, etc.), an aralkylgroup (e.g. a C₇₋₁₀ aralkyl group such as benzyl, phenethyl, etc.,preferably a phenyl-C₁₋₄ alkyl group etc.), a heterocyclic group (e.g.the same substituent as those in the above described “heterocyclicgroup” as the substituent of the “optionally substituted hydrocarbongroup” represented by R^(a1), etc.), etc. Said the lower alkyl group,the cycloalkyl group, the aryl group, the aralkyl group and theheterocyclic group may have a substituent and examples of thesubstituent include e.g. a hydroxyl group, an optionally substitutedamino group [said amino group may have 1 to 2 substituents (e.g. a loweralkyl group (e.g. a C₁₋₆ alkyl group such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group(e.g. a C₁₋₆ alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc.,an aryl-carbonyl such as benzoyl, etc., a C₁₋₆ alkylsulfonyl such asmethylsulfonyl, ethylsulfonyl, etc.), etc.)], a halogen atom (e.g.fluorine, chlorine, bromine, iodine, etc.), a nitro group, a cyanogroup, a lower alkyl group optionally substituted with 1 to 5 halogenatoms (e.g. fluorine, chlorine, bromine, iodine, etc.), a lower alkoxygroup optionally substituted with 1 to 5 halogen atoms (e.g. fluorine,chlorine, bromine, iodine, etc.), etc. Said lower alkyl group includee.g. a C₁₋₆ alkyl group such as methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, etc. and inparticular methyl, ethyl, etc. are preferable. Said lower alkoxy groupinclude e.g. a C₁₋₆ alkoxy group such as methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc. and inparticular methoxy, ethoxy, etc. are preferable. It is preferable thatone, two or three substituents, more preferably two substituents arepresent.

The “N,N-di-substituted carbamoyl group” is a carbamoyl group having twosubstituents on the nitrogen atom. Examples of one of the substituentsinclude the same as those of the above described “N-mono-substitutedcarbamoyl group” and examples of the other substituent include e.g. alower alkyl group (e.g. a C₁₋₆ alkyl group such as methyl, ethyl,propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), a C₃₋₆cycloalkyl group (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,etc.), a C₇₋₁₀ aralkyl group (e.g. benzyl, phenethyl, etc., preferablyphenyl-C₁₋₄ alkyl group, etc.), etc. In addition, two substituents ofthe “N,N-di-substituted carbamoyl group” may form a cyclic amino-grouptogether with a nitrogen atom. Examples of said cyclic amino-carbamoylgroup include e.g. 3- to 8-membered (preferably 5- to 6-membered) cyclicamino-carbamoyl group such as 1-azetidinylcarbonyl,1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 4-morpholinylcarbonyl,1-piperazinylcarbonyl and 1-piperazinylcarbonyl which may have at the4-position a lower alkyl group (e.g. a C₁₋₆ alkyl group such as methyl,ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), anaralkyl group (e.g. a C₇₋₁₀ aralkyl group such as benzyl, phenethyl,etc.), an aryl group (e.g. a C₆₋₁₀ aryl group such as phenyl,1-naphthyl, 2-naphthyl, etc.), etc.

Examples of the substituent in the “optionally substituted thiocarbamoylgroup” include the same substituent as those in the above described“optionally substituted carbamoyl group”.

Examples of the “sulfamoyl group which may be substituted” include anunsubstituted-sulfamoyl group, a N-mono-substituted sulfamoyl group anda N,N-di-substituted sulfamoyl group.

The “N-mono-substituted sulfamoyl group” is a sulfamoyl group having onesubstituent at the nitrogen atom, and examples of the substituentinclude those mentioned as the substituent of N-mono-substitutedcarbamoyl group. The “N,N-di-substituted sulfamoyl group” is a sulfamoylgroup having two substituents at the nitrogen atom, and examples of thesubstituent include those mentioned as the substituent of theN,N-di-substituted carbamoyl group.

Examples of the optionally esterified carboxyl groupinclude a freecarboxyl group as well as a lower alkoxycarbonyl group, anaryloxycarbonyl group, an aralkyloxycarbonyl group, etc.

Examples of the “lower alkoxycarbonyl group” include e.g. a C₁₋₆alkoxy-carbonyl group such as methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl,isopentyloxycarbonyl, neopentyloxycarbonyl, etc. Among them, a C₁₋₃alkoxy-carbonyl group such as methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, etc. are preferable.

Examples of the “aryloxycarbonyl group” include e.g. a C₇₋₁₂aryloxy-carbonyl group such as phenoxycarbonyl, 1-naphthoxycarbonyl,2-naphthoxycarbonyl, etc.

Examples of the “aralkyloxycarbonyl group” include e.g. a C₇₋₁₀aralkyloxy-carbonyl group, etc. (preferably, a C₆₋₁₀ aryl-C₁₋₄alkoxy-carbonyl, etc.) such as benzyloxycarbonyl, phenethyloxycarbonyl,etc.

Said “aryloxycarbonyl group” and “aralkyloxycarbonyl group” may besubstituted. Examples of the substituent include the same kind andnumber of the substituents of the aryl group and aralkyl group asexamples of the substituent for the above described N-mono-substitutedcarbamoyl group.

Examples of the “acyl group derived from a sulfonic acid” as thesubstituent include a sulfonyl group substituted by a hydrocarbon group,and preferably include an acyl group such as C₁₋₁₀ alkyl-sulfonyl, C₂₋₆alkenyl-sulfonyl, C₂₋₆ alkynyl-sulfonyl, C₃₋₉ cyclo-alkyl-sulfonyl, C₃₋₉cyclo-alkenyl-sulfonyl, C₆₋₁₄ aryl-sulfonyl, C₇₋₁₀ aralkyl-sulfonyl etc.Examples of the C₁₋₁₀ alkyl include, for example, methyl, ethyl, propyl,isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, etc.Examples of the C₂₋₆ alkenyl include, for example, vinyl, allyl,1-propenyl, isopropenyl, 2-butenyl, 3-butenyl, 2-hexenyl, etc. Examplesof C₂₋₆ alkynyl include, for example, ethynyl, 2-propynyl, 2-butynyl,5-hexynyl, etc. Examples of the C₃₋₉ cyclo-alkyl include, for example,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc.

Examples of the C₃₋₉ cyclo-alkenyl include, for example,1-cyclopenten-1-yl, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl,3-cyclohexen-1-yl, 3-cycloocten-1-yl, etc. Examples of the C₆₋₁₄ arylinclude, for example, phenyl, 1-naphthyl, 2-naphthyl, etc. Examples ofthe C₇₋₁₀ aralkyl-sulfonyl include, for example, benzyl, phenethyl, etc.

These hydrocarbon groups bonded to the sulfonyl may be substituted.Examples of the substituent include, for example, hydroxyl, amino whichmay be substituted [The amino may be substituted with 1 or 2substituents (Examples of the substituent include lower alkyl group(e.g. C₁₋₆ alkyl etc. such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group (e.g., C₁₋₆alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., arylcarbonyl such as benzoyl, etc., C₁₋₆ alkyl-sulfonyl such asmethylsulfonyl, ethylsulfonyl, etc.)), halogen atom (for example,fluorine, chlorine, bromine, iodine, etc.), nitro group, cyano group,lower alkyl group which may be substituted by 1 to 5 halogen atom (forexample, fluorine, chlorine, bromine, iodine, etc.), lower alkyl groupwhich may be substituted by 1 to 5 halogen atom (for example, fluorine,chlorine, bromine, iodine, etc.) etc. Examples of the lower alkyl groupinclude, for example, C₁₋₆ alkyl group such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl,etc., and preferably include methyl, ethyl, etc. Examples of the loweralkoxy group include, for example, C₁₋₆ alkoxy group such as methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy,tert-butoxy, etc, and preferably include methoxy, ethoxy, etc. Thesesubstituents may be the same or different from each other, and one, twoor three substituents, preferably one or two substituents may bepresent.

Examples of the “acyl group derived from a carboxylic acid” as thesubstituent include a carbonyl group having a hydrogen atom or onesubstituent which the above described “N-mono-substituted carbamoylgroup” have on the nitrogen atom, etc., preferably, a C₁₋₆ alkanoyl suchas formyl, acetyl, trifluoroacetyl, propionyl, butyryl, isobutyryl,pivaloyl, etc., an acyl of an aryl-carbonyl such as benzoyl etc.Examples of the alkyl in “alkyl-sulfinyl group which may be substituted”as a substituent include a lower alkyl, for example, a C₁₋₆ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,hexyl, etc.

Examples of the aryl in “aryl-sulfinyl group which may be substituted”as a substituent include, for example, a C₆₋₁₄ aryl group etc., such asphenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, etc. Examplesof the substituent of the alkyl group or the aryl group include a loweralkoxy group (e.g. a C₁₋₆ alkoxy group etc, such as methoxy, ethoxy,propoxy, etc.), a halogen atom (e.g., fluorine, chlorine, bromine,iodine, etc.), a lower alkyl group (a C₁₋₆ alkyl group etc., such asmethyl, ethyl, propyl, etc.), amino, hydroxyl, cyano, amidino, etc. Oneor two of these substituents may be present at any substitutableposition.

Examples of “hydrocarbon group which may be substituted” and“non-aromatic heterocyclic group which may be substituted” shown asR^(a2) include the same ones as “hydrocarbon groups which may besubstituted” and “non-aromatic heterocyclic group which may besubstituted” shown by R^(a1), respectively. Among them, a C₂₋₆ alkylwhich may be substituted and a C₃₋₈ cycloalkyl which may be substitutedare preferable.

When R^(a1) and R^(a2) are bind to each other together with the adjacentnitrogen atom to form a heterocyclic ring group which may besubstituted, the heterocyclic ring contains one nitrogen atom, and mayfurther contain a nitrogen atom, an oxygen atom and a sulfur atom.Examples of the ring include, for example, a cyclic amino group such amonocyclic ring as 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl,1-homopiperidinyl, heptamethyleneimino, 1-piperazinyl,1-homopiperazinyl, 4-morpholinyl, 4-thiomorpholinyl, etc., such a fusedring as 2-isoindolinyl, 1,2,3,4-tetrahydro-2-isoquinolyl,1,2,4,5-tetrahydro-3H-3-benzoazepine-3-yl, etc., such a spiro ring asinden-1-spiro-4′-piperidin-1′-yl, etc. The cyclic amino group may have 1to 5 substituents, preferably 1 to 3 substituents at chemicallysubstitutable positions on the ring.

Examples of the substituent include a hydroxyl group, a cyano group, anitro group, an amino group, an oxo group, a halogen atom and a grouprepresented by the formula: —YR^(aa), wherein R^(aa) is a hydrocarbongroup which may be substituted or a heterocyclic group which may besubstituted, and Y is a bond (a single bond), —CR^(ab)R^(ac)—, —COO—,—CO—, —CR^(ab)(OH)—, —CO—NR^(ab), —CS—NR^(ab)—, —CO—S—, —CS—S—,—CO—NR^(ab)—CO—NR^(ac)—, —C(═NH)—NR^(ab)—, —NR^(ab)—, —NR^(ab)—CO—,—NR^(ab)—CS—, —NR^(ab)—CO—NR^(ac), —NR^(ab)—CS—NR^(ac)—, —NR^(ab)—CO—O—,—NR^(ab)CS—O—, —NR^(ab)CO—S—, —NR^(ab)—CS—S—, —NR^(ab)—(═NH)—NR^(ac)—,NR^(ab)—SO₂—, —NR^(ab—NR) ^(ac)—, —O—, —O—CO—, —O—CS—, —O—CO—O,—O—CO—NR^(ab)—, —O—C(═NH)—NR^(ab)—, —S—, —SO—, —SO₂—, —CR^(ab)R^(ac)—S—,CR^(ab)R^(ac)—SO₂—, —SO₂—NR^(ab)—, —S—CO—, —S—CS—, —S—CO—NR^(ab)—,—S—CS—NR^(ab)—, —S—C(═NH)—NR^(ab)—, wherein each of R^(ab) and R^(ac) isa hydrogen atom, an alkyl group which may be substituted, an alkenylgroup which may be substituted, an alkynyl group which may besubstituted, an aryl group which may be substituted, a cycloalkyl groupwhich may be substituted, a cycloalkenyl group which may be substituted,a heterocyclic group which may be substituted, an acyl group derivedfrom sulfonic acid, an acyl group derived from carboxylic acid, etc.

Examples of the “hydrocarbon group” in the “optionally substitutedhydrocarbon group” represented by R^(aa) include e.g. an aliphatichydrocarbon group, an alicyclic hydrocarbon group and an aryl group,etc. Examples of the aliphatic hydrocarbon group, the alicyclichydrocarbon group and the aryl group include those represented byR^(a1). Examples of the substituent of the “hydrocarbon group optionallysubstituted” include the same substituent as those in the abovedescribed “hydrocarbon group which may be substituted” represented byR^(a1).

Examples of the heterocyclic group in the “heterocyclic group which maybe substituted” represented by R^(aa) include the same heterocyclicgroup as those of “heterocyclic group which may be substituted”represented by R^(a3) mentioned below. Examples of the “substituent” inthe “heterocyclic group which may be substituted” include thosementioned as the “substituent” in a “non-aromatic heterocyclic groupwhich may be substituted” represented by R^(a1).

Examples of the “alkyl group which may be substituted”, “alkenyl groupwhich may be substituted”, “alkynyl group which may be substituted”,“aryl group which may be substituted”, “cyclo-alkyl group which may besubstituted”, “cyclo-alkenyl group which may be substituted”,“heterocyclic group which may be substituted”, “acyl group derived fromsulfonic acid”, and “acyl group derived from carboxylic acid”, each ofwhich is represented by R^(ab) and R^(ac), include those mentioned asthe substituent in the “hydrocarbon group which may be substituted”represented by R^(a1).

R^(a1) and R^(a2) are preferable to bind to each other together with thenitrogen atom to form a heterocyclic ring which may be substituted. Morepreferably, NR^(a1)R^(a2) is a group represented by the formula:

(wherein Y^(a) and R^(aa) have the same meanings given above). In theabove, while Y^(a) and R^(aa) have the same meanings given above, R^(aa)is more preferably an aryl group which may be substituted or aheterocyclic group which may be substituted.

Examples of a “cyclic hydrocarbon group” in the “cyclic hydrocarbongroup which may be substituted”represented by R^(a3) include e.g. analicyclic hydrocarbon group, an aryl group, etc.

Examples of the “alicyclic hydrocarbon group” include e.g. a saturatedor unsaturated alicyclic hydrocarbon group such as a cycloalkyl group, acycloalkenyl group, a cycloalkanedienyl group, etc., preferably acycloalkyl group.

Examples of the “cycloalkyl group” include e.g. a C₃₋₉ cycloalkyl,(preferably a C₃₋₈ acycloalkyl, etc.) such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, etc., anda fused ring such as 1-indanyl, 2-indanyl, etc.

Examples of the “cycloalkenyl group” include e.g. a C₃₋₆ cycloalkenylgroup such as 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl,3-cyclohexen-1-yl, 1-cyclobuten-1-yl, 1-cyclopenten-1-yl, etc.

Examples of the “cycloalkanedienyl group” include e.g. a C₄₋₆cycloalkanedienyl group such as 2,4-cyclopentadien-1-yl,2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, etc.

Examples of the “aryl group” include e.g. a monocyclic or fusedpolycyclic aromatic hydrocarbon group. Among them, a C₆₋₁₄ aryl groupsuch as phenyl, naphthyl, anthryl, phenathryl, acenaphthyl, etc. ispreferable. In particular, phenyl, 1-naphthyl, 2-naphthyl, etc. arepreferable.

Examples of the substituent in the “cyclic hydrocarbon group which maybe substituted” represented by R^(a3) include those mentioned as thesubstituent in the “hydrocarbon group which may be substituted”represented by R^(a1). The substituent include, for example, a phenylgroup, a phenyl group which may be substituted by a C₁₋₆ alkyl groupsuch as a tolyl group, etc., a naphthyl group, etc., when the cyclichydrocarbon group is alicyclic hydrocarbon group, and is preferably, forexample a halogen atom (e.g., chlorine atom, fluorine atom, etc.), aC₁₋₆ alkyl group (methyl, ethyl, propyl, isopropyl, butyl, isobutyl,t-butyl, pentyl, hexyl, etc.), a C₁₋₆ alkoxy group (e.g., methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, etc.), a C₃₋₆ cyclo-alkyl group(e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), ahalogenated-C₁₋₆ alkyl group (trifluoromethyl, etc.), a halogenated-C₁₋₆alkoxy group (trifluoromethyloxy, etc.), a C₁₋₆ alkyl-thio group(methylthio, ethylthio, etc.), a C₁₋₆ alkyl-sulfonyl group(methylsulfonyl, ethylsulfonyl, etc.), cyano group, nitro group, etc.,when the cyclic hydrocarbon group is an aryl group.

Examples of the heterocyclic group in the “optionally substitutedheterocyclic group” represented by R^(a3) include e.g. an aromaticheterocyclic group, a saturated or unsaturated non-aromatic heterocyclicgroup (an alicyclic heterocyclic group) etc., which contains, at leastone hetero-atom (preferably 1 to 4 hetero-atoms, more preferably 1 to 2hetero-atoms) consisting of 1 to 3 kinds of hetero-atoms (preferably 1to 2 kinds of hetero-atoms) selected from an oxygen atom, a sulfur atom,a nitrogen atom, etc. as atom(s) which form a ring (ring atoms).

Examples of the “aromatic heterocyclic group” include an aromaticmonocyclic heterocyclic group such as a 5- to 6-membered aromaticmonocyclic heterocyclic group, etc. (e.g. furyl, thienyl, pyrrolyl,oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, etc.); an aromatic fused heterocyclicgroup such as a 8- to 12-membered aromatic fused heterocyclic group(e.g. benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl,1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzoisooxazolyl,benzothiazolyl, benzopyranyl, 1,2-benzoisothiazolyl, benzodioxolyl,benxoimidazolyl, 2,1,1-benzoxadiazolyl, 1H-benzotriazolyl, quinolyl,isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl,naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl,β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl,phenazinyl, phenoxathinyl, thianthrenyl, phenanthridinyl,phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl,pyrazolo[1,5-a]pyridyl, pyrazolo[3,4-b]piridyl, imidazo[1,2-a]pyridyl,imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl,imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl,1,2,4-triazolo[4,3-b]pyridazinyl, etc.); etc., preferably, aheterocyclic group consisting of the above-mentioned 5- or 6-memberedaromatic monocyclic heterocyclic group fused with a benzene ring or aheterocyclic group consisting of the above-mentioned 5- or 6-memberedaromatic monocyclic heterocyclic group fused with the same or differentabove-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group,etc.

Examples of the “non-aromatic heterocyclic group” include a 3- to8-membered (preferably 5- or 6-membered) saturated or unsaturated(preferably saturated) non-aromatic heterocyclic group (alicyclicheterocyclic group) such as oxiranyl, azetidinyl, oxetanyl, thiethanyl,pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl,tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.

Examples of the substituent in the “heterocyclic group which may besubstituted” represented by R^(a3) include those mentioned as thesubstituent “non-aromatic heterocyclic group which may be substituted”represented by R^(a1). R^(a3) is preferably a phenyl group which may besubstituted.

Examples of the “hydrocarbon group which may be substituted” representedby R^(a4) include the same “hydrocarbon group which may be substituted”represented by R^(a1) of the “heterocyclic group which may besubstituted” represented by R^(a4) include the same “heterocyclic groupwhich may be substituted” represented by R^(a3).

Examples of the “alkoxy group” in “alkoxy group which may besubstituted” represented by R^(a4) preferably include, for example, aC₁₋₆ alkoxy such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec-butoxy, tert-butoxy, etc. Examples of the “substituent”include, for example, a cycloalkyl group (e.g. a C₃₋₆ cycloalkyl groupsuch as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), an arylgroup (e.g. a C₆₋₁₀ aryl group, etc., such as phenyl, 1-naphthyl,2-naphthyl, etc.), an aralkyl group (e.g. a C₇₋₁₀ aralkyl group forexample, such as benzyl, phenethyl, etc., preferably a phenyl-C₁₋₄ alkylgroup, etc., etc.), a heterocyclic group (e.g., a “heterocyclic group”mentioned as the substituent in the “hydrocarbon group which may besubstituted” represented by R^(a1)), etc. Each of the lower alkyl group,the cycloalkyl group, the aryl group, the aralkyl group and theheterocyclic group may be substituted. Examples of the substituentsinclude, for example, a hydroxyl group, an amino group which may besubstituted [the amino group may have 1 or 2 substituents such as alower alkyl group (a C₁₋₆ alkyl group such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group(a C₁₋₆ alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., anaryl carbonyl such as benzoyl, etc. for example, a C₁₋₆ alkyl-sulfonyletc. such as methyl-sulfonyl, ethyl-sulfonyl etc.)], a halogen atom(e.g. fluorine, chlorine, bromine, iodine etc.), a nitro group, a cyanogroup, a lower alkyl group (which may be substituted by 1 to 5 halogenatoms (e.g. fluorine, chlorine, bromine, iodine etc.)), a lower alkoxygroup (which may be substituted by 1 to 5 halogen atoms (e.g. fluorine,chlorine, bromine, iodine etc.)), etc. Examples of the lower alkyl groupinclude a C₁₋₆ alkyl group such as methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, etc., and inparticular methyl, ethyl, etc. are preferable. Examples of the loweralkoxy group include, for example, a C₁₋₆ alkoxy group etc. such asmethoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy,tert-butoxy, etc., and in particular methoxy, ethoxy, etc. arepreferable. The above described lower alkoxy group may have 1 or 2 to 3(preferably 1 or 2) substituents. When the alkoxy group has 2 or 3substituents, these substituents may be the same or different.

Examples of the “aryl group” in “aryloxy group which may be substituted”represented by R^(a4) include, for example, a C₆₋₁₄ aryl group such asphenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, etc. Examplesof the substituent include, for example, a lower alkoxy group (e.g. aC₁₋₆ alkoxy group such as methoxy, ethoxy, propoxy, etc.), a halogenatom (e.g., fluorine, chlorine, bromine, iodine, etc.), a lower alkylgroup (for example a C₁₋₆ alkyl group such as methyl, ethyl, propyl,etc.), an amino group, a hydroxyl group, a cyano group, an amidinogroup, etc. These optional aryloxy groups may have 1 or 2 at anypossible position.

Examples of the “substituent” in “amino group which may be substituted”represented by R^(a4) include, for example, a lower alkyl group (e.g., aC₁₋₆ alkyl group such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group (a C₁₋₆ alkanoyl(e.g., formyl, acetyl, propionyl, pivaloyl, etc.), benzoyl, etc.), aC₁₋₆ alkoxy-carbonyl which may be halogenated (e.g.,trifluoromethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl,trichloromethoxy carbonyl, 2,2,2-trichloroethoxy carbonyl, etc.), etc.In addition, the “amino group” in the “optionally substituted aminogroup” as the substituent may be substituted with an optionallysubstituted imidoyl group (e.g., a C₁₋₆ alkylimidoyl, formimidoyl,amidino, etc.), etc. and two substituents of the “amino group” may forma cyclic amino group together with a nitrogen atom. Examples of saidcyclic amino group include e.g. a 3- to 8-membered (preferably 5- to6-membered) cyclic amino group such as 1-azetidinyl, 1-pyrrolidinyl,1-piperidinyl, 4-morpholinyl, 1-piperazinyl and 1-piperazinyl which mayhave at the 4-position a lower alkyl group (e.g. a C₁₋₆ alkyl group etc.such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl,etc.), an aralkyl group (e.g. a C₇₋₁₀ aralkyl group etc. such as benzyl,phenethyl, etc.), an aryl group (e.g. a C₆₋₁₀ aryl group etc. such asphenyl, 1-naphthyl, 2-naphthyl, etc.), etc.

R^(a4) is preferably a C₁₋₃ alkyl, a phenyl which may be substituted,3-pyridyl, 4-pyridyl, etc.

Examples of the hydrocarbon group represented by R^(a5) include thosementioned as a “hydrocarbon group” in the “hydrocarbon group which maybe substituted” represented by R^(a1). The preferable examples of thehydrocarbon group include a lower alkyl group having 1 to 4 carbon atomssuch as methyl, ethyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl,tert-butyl, etc.

Examples of the counter anion represented by Y^(a) include, for example,Cl⁻, Br⁻, I⁻, NO₃ ⁻, SO₄ ²⁻, PO₄ ³⁻, CH₃SO₃ ⁻, etc.

Examples of the divalent aliphatic hydrocarbon group in the divalentalipahatic hydrocarbon group which may be substituted by group otherthan an oxo group represented by Ea include, for example, a C₁₋₆alkylene such as methylene, ethylene, etc., a C₂₋₆ alkenylene such asethenylene, etc., a C₂₋₆ alkynylene such as ethynylen, etc., and amongthem, a C₂₋₅ alkylene is more preferable and trimethylene is the mostpreferable.

The substituent of the divalent hydrocarbon group is a substituent otherthan an oxo group, and examples of the substituents include, forexample, an alkyl group which may be substituted, an aryl group whichmay be substituted, a cycloalkyl group or a cycloalkenyl group which maybe substituted, a carboxyl group which may be esterified, a carbamoylgroup or a thiocarbamoyl group which may be substituted, an amino groupwhich may be substituted, a hydroxyl group which may be substituted, athiol (i.e. mercapto) group which may be substituted, an acyl groupderived from carboxylic acid, an acyl group derived from sulfonic acid,a halogen (e.g., fluorine, chlorine, bromine, etc.), nitro, cyano, etc.The divalent hydrocarbon group may have 1 to 3 substituents. Each of thealkyl group or the aryl group which may be substituted, the cycloalkylgroup or the cycloalkenyl group which may be substituted, the carboxylgroup which may be esterified, the carbamoyl group which may besubstituted, the thiocarbamoyl group which may be substituted, the aminogroup which may be substituted, the hydroxyl group which may besubstituted, the thiol group (i.e. mercapto group) which may besubstituted, the acyl group derived from carboxylic acid and the acylgroup derived from sulfonic acid include those mentioned as thesubstituent in “heterocyclic group which may be substituted” representedby R^(a3).

Examples of the C₁₋₃ aliphatic hydrocarbon group in “divalentC₁₋₃aliphatic hydrocarbon group which may be substituted” represented byQ^(a) and R^(a) inclde a divalent aliphatic hydrocarbon group having 1to 3 carbon atoms in the divalent aliphatic ydrocarbon group in divalentaliphatic hydrocarbon group which may be substituted by a group otherthan an oxo group represented by E^(a).

Examples of the substituent in the “divalent C₁₋₃ aliphatic ydrocarbongroup which may be substituted”represented by Q^(a) and R^(a) includethose mentioned as the substituent in divalent aliphatic ydrocarbongroup which may be substituted by a group other than an oxo grouprepresented by E^(a).

J^(a) is a methine or a nitrogen atom, and methine is preferable.

G^(a1) is a bond, CO or SO₂, and CO or SO₂ is preferable.

Ga² is CO, SO₂, NHCO, CONH or OCO, and among them, CO, NHCO and OCO arepreferable.

The compound of the formula (I) or a salt thereof may be an hydrate.

Following compounds are preferable.

(I-1) A compound as shown in the above (1), wherein R^(a1) is a hydrogenatom, a hydrocarbon group selected from Group a2 which may besubstituted by member(s) selected from Group a1, a 3- to 8-memberedsaturated or unsaturated non-aromatic heterocyclic group which may besubstituted by member(s) selected from Group a1; R^(a2) is a hydrocarbongroup selected from Group a2 which may be substituted by member(s)selected from Group a1 or a 3- to 8-membered saturated or unsaturatednon-aromatic heterocyclic group which may be substituted by member(s)selected from Group a1, or R^(a1) and R^(a2) may combine each othertogether with A^(a) to form a heterocyclic group selected from Group a4which may be substituted by member(s) selected from Group a3; A^(a) is Nor N⁺—R^(a5).Y^(a)— (Y^(a)— is Cl⁻, Br⁻, I⁻, NO₃ ⁻, SO₄ ²⁻, PO₄ ³⁻ orCH₃SO₃ ⁻; R^(a5) is a hydrocarbon group selected from Group a2); R^(a3)is a cyclic hydrocarbon group selected from Group a5 which may besubstituted by member(s) selected from Group a1 or a heterocyclic groupselected from Group a6 which may be substituted by member(s) selectedfrom Group a1; R^(a4) is a hydrogen atom, a hydrocarbon group selectedfrom Group a2 which may be substituted by member(s) selected from Groupa1, a heterocyclic group, selected from Group a6 which may besubstituted by member(s) selected from Group a1, a C₁₋₆ alkoxy groupwhich may be substituted by member(s) selected from Group a7, a C₆₋₁₄aryloxy group which may be substituted by member(s) selected from Groupa8, an amino group which may be substituted by member(s) selected fromGroup a9 or a cyclic-amino group selected from Group a10; E^(a) is adivalent aliphatic hydrocarbon group selected from Group a12 which maybe substituted by member(s) other than oxo group(s) and selected fromGroup a11; each of Q^(a) and R^(a) is a bond or a divalent C₁₋₃aliphatic ydrocarbon group selected from Group a13 which may besubstituted by member(s) selected from Group a11.

Group a1

(1) a C₁₋₆ alkyl group which may be substituted by member(s) selectedfrom Group a14, (2) a C₂₋₆ alkenyl group which may be substituted bymember(s) selected from Group a14, (3) a C₂₋₆ alkynyl group which may besubstituted by member(s) selected from Group a14, (4) a C₆₋₁₄ aryl groupwhich may be substituted by member(s) selected from Group a14, (5) aC₃₋₇ cycloalkyl group which may be substituted by member(s) selectedfrom Group a14, (6) a C₃₋₆ cycloalkenyl group which may be substitutedby member(s) selected from Group a14, (7) a heterocyclic group selectedfrom Group a16 which may be substituted by member(s) selected from Groupa15, (8) an amino group which may be substituted by a C₁₋₆alkyl-imidoyl(s), formyl-imidoyl(s), amidino(s) or member(s) selectedfrom Group a17, (9) a cyclic-amino group selected from Group a10, (10)an imidoyl group which may be substituted by member(s) selected fromGroup a17, (11) an amidino group which may be substituted by member(s)selected from Group a17, (12) a hydroxyl group which may be substitutedby a member selected from Group a17, (13) a thiol group which may besubstituted by a member selected from Group a17, (14) a carboxyl group,(15) a C₁₋₆ alkoxy-carbonyl group which may be substituted by member(s)selected from Group a18, (16) a C₇₋₁₂ aryloxy-carbonyl group which maybe substituted by member(s) selected from Group a18, (17) a C₇₋₁₀aralkyl-oxy-carbonyl group which may be substituted by member(s)selected from Group a18, (18) a carbamoyl group, (19) a mono-substitutedcarbamoyl group which may be substituted by a member selected from Groupa19, (20) a di-substituted carbamoyl group substituted by a memberselected from Group a19 and a member selected from Group a20, (21) acyclic-aminocarbamoyl group selected from Group a21, (22) athiocarbamoyl group, (23) a mono-substituted thiocarbamoyl group whichmay be substituted by a member selected from Group a19, (24) adi-substituted thiocarbamoyl group substituted by a member selected fromGroup a19 and a member selected from Group a20, (25) acyclic-aminothiocarbamoyl group selected from Group a21, a sulfamoylgroup, (26) a N-mono-substituted sulfamoyl group substituted by a memberselected from Group a19, (27) a N,N-di-substituted sulfamoyl groupsubstituted by a member selected from Group a19 and a member selectedfrom Group a20, (28) a cyclic-amino-sulfonyl group selected from Groupa22, (29) a halogen atom, (30) a cyano group, (31) a nitro group, (32)an acyl group derived from a sulfonic acid selected from Group a22, (33)a formyl group, (34) a C₂₋₆ alkanoyl group, (35) a C₇₋₁₂ aryl-carbonylgroup, (36) a C₁₋₆ alkyl-sulfinyl group which may be substituted bymember(s) selected from Group a23 and (37) a C₆₋₁₄ aryl-sulfinyl groupwhich may be substituted by member(s) selected from Group a23

Group a2

(1) a C₁₋₁₀ alkyl group, (2) a C₂₋₆ alkenyl group, (3) a C₂₋₆ alkynylgroup, (4) a C₃₋₉ cycloalkyl group which may be condensed with benzene,(5) a C₃₋₆ cycloalkenyl group, (6) a C₄₋₆ cycloalkadienyl group and (7)a C₆₋₁₄ aryl group

Group a3

(1) a hydroxy group, (2) a cyano group, (3) a nitro group, (4) an aminogroup, (5) an oxo group, (6) a halogen atom and (7) a group representedby the formula: —B¹R^(aa) [wherein R^(aa) is a hydrocarbon groupselected from Group a2 which may be substituted by member(s) selectedfrom Group a1, or a heterocyclic group selected from Group a6 which maybe substituted by member(s) selected from Group a1, B¹ is a bond (asingle bond), —CR^(ab)R^(aC)—, —COO—, —CO—, CR^(ab)(OH)—,—CR^(ab)R^(ac)—S—, —CR^(ab)R^(ac)—SO₂—, —CO—NR^(ab)—, —CS—NR^(ab)—,—CO—S—, —CS—S—, —CO—NR^(ab)—CO—NR^(ac)—, —C(═NH)—NR^(ab)—, —NR^(ab)—,—NR^(ab)—CO—, —NR^(ab)—CS—, —NR^(ab)—CO—NR^(aC)—, —NR^(ab)—CS—NR^(aC)—,—NR^(ab)—CS—O—, —NR^(ab)—CO—S—, —NR^(ab)—CS—S—,—NR^(ab)—C(═NH)—NR^(aC)—, —NR^(ab)—SO₂—, —NR^(ab)—NR^(aC)—, —O—, —O—CO—,—O—CS—, —O—CO—O—, —O—CO—NR^(ab)—, —O—C(═NH)—NR^(ab)—, —S—, —SO—, —SO₂—,—SO₂—NR^(ab)—, —S—CO—, —S—CS—, —S—CO—NR^(ab)—, —S—CS—NR^(ab)— and—S—C(═NH)—NR^(ab)— (wherein each of R^(ab) and R^(ac) is a hydrogenatom, a C₁₋₆ alkyl group which may be substituted by member(s) selectedfrom Group a14, a C₂₋₆ alkenyl group which may be substituted bymember(s) selected from Group a14, a C₂₋₆ alkynyl group which may besubstituted by member(s) selected from Group a14, a C₆₋₁₄ aryl groupwhich may be substituted by member(s) selected from Group a14, a C₃₋₇cycloalkyl group which may be substituted by member(s) selected fromGroup a14, a C₃₋₆ cycloalkenyl group which may be substituted bymember(s) selected from Group a14, a heterocyclic group selected fromGroup a6 which may be substituted by member(s) selected from Group a1,an acyl group derived from a sulfonic acid selected from Group a22, aC₁₋₆ alkanoyl, and a C₇₋₁₂ aryl-carbonyl group)]

Group a4

(1) a monocyclic heterocyclic group, (2) a heterocyclic group condensedwith benzene and (3) a heterocyclic spiro compound, each of whichcontains one nitrogen atom and may further contain one or more atomsselected from the group consisting of a nitrogen atom, a oxygen atom anda sulfur atom

Group a5

(1) a C₃₋₉ cycloalkyl which may be condensed with benzene, (2) a C₃₋₆cycloalkenyl group, (3) a C₄₋₆ cycloalkadienyl group and (4) a C₆₋₁₄aryl group

Group a6

(1) a 5- to 6-membered aromatic monocyclic heterocyclic group selectedfrom Group a24, (2) a 8- to 12-membered aromatic condensed heterocyclicgroup selected from Group a26 and (3) a 3- to 8-membered saturated orunsaturated non-aromatic heterocyclic group (aliphatic heterocyclicgroup) selected from Group a25, each of which contains at least onehetero atom of one to three hetero atoms selected from the groupconsisting of an oxygen atom, a sulfur atom and a nitrogen atom etc. asa ring formed of atoms (ring atoms)

Group a7

a C₃₋₆ cycloalkyl group which may be substituted by member(s) selectedfrom Group a18, a C₆₋₁₀ aryl group which may be substituted by member(s)selected from Group a18, a C₇₋₁₀ aralkyl group which may be substitutedby member(s) selected from Group a18 and a heterocyclic group selectedfrom Group a16 which may be substituted by member(s) selected from Groupa18

Group a8

a C₁₋₆ alkoxy group, a halogen atom, a C₁₋₆ alkyl group, an amino group,a hydroxyl group, a cyano group and an amidino group

Group a9

(1) a C₁₋₆ alkyl group, (2) a C₁₋₆ alkanoyl, (3) benzoyl, (4) a C₁₋₆alkoxy-carbonyl which may be substituted by halogen(s), (5) a C₁₋₆alkyl-imidoyl, (6) formyl-imidoyl and (7) amidino

Group a10

(1) 1-azetidinyl, (2) 1-pyrrolidinyl, (3) 1-piperidinyl, (4)4-morpholinyl and (5) a 1-piperazinyl which may be substituted bymember(s) selected from Group a27

Group a11

(1) a C₁₋₆ alkyl group which may be substituted by member(s) selectedfrom Group a14, (2) a C₆₋₁₄ aryl group which may be substituted bymember(s) selected from Group a14, (3) a C₃₋₇ cycloalkyl group which maybe substituted by member(s) selected from Group a14, (4) a C₃₋₆cycloalkenyl group which may be substituted by member(s) selected fromGroup a14, (5) a carboxyl group, (6) a C₁₋₆ alkoxy-carbonyl group whichmay be substituted by member(s) selected from Group a18, (7) a C₇₋₁₂aryloxy-carbonyl group which may be substituted by member(s) selectedfrom Group a18, (8) a C₇₋₁₀ aralkyl-oxy-carbonyl group which may besubstituted by member(s) selected from Group a18, (9) a carbamoyl group,(10) a mono-substituted carbamoyl group substituted by a member selectedfrom Group a19, (11) a di-substituted carbamoyl group substituted by amember selected from Group a19 and a member selected from Group a20,(12) a cyclic-aminocarbamoyl group selected from Group a21, (13) athiocarbamoyl group, (14) a mono-substituted thiocarbamoyl groupsubstituted by a member selected from Group a19, (15) a di-substitutedthiocarbamoyl group substituted by a member selected from Group a19 anda member selected from Group a20, (16) a cyclic-aminothiocarbamoyl groupselected from Group a21, (17) an amino group which may be substituted bya C₁₋₆ alkyl-imidoyl(s), formyl-imidoyl(s), amidino(s) or member(s)selected from Group a17, (18) a cyclic-amino group selected from Groupa10, (19) a hydroxyl group which may be substituted by a member selectedfrom Group a17, (20) a thiol group which may be substituted by a memberselected from Group a17, (21) a C₁₋₆ alkanoyl group, (22) a C₇₋₁₂aryl-carbonyl group, (23) an acyl group derived from a sulfonic acidselected from Group a22, (24) a halogen, (25) nitro and (26) cyano

Group a12

a C₁₋₆ alkylene, a C₂₋₆ alkenylene and a C₂₋₆ alkynylene

Group a13

a C₁₋₃ alkylene, a C₂₋₃ alkenylene and a C₂₋₃ alkynylene

Group a14

(1) a C₁₋₆ alkoxy group which may be substituted by halogen(s), (2) aphenoxy which may be substituted by halogen(s) or carbamoyl(s), (3) ahalogen atom, (4) a C₁₋₆ alkyl group, (5) a C₁₋₄ alkyl group substitutedby halogen(s), (6) C₃₋₈ cycloalkyl, (7) an amino group, (8) an aminogroup substituted by one or two members selected from the groupconsisting of carbamoyl, C₁₋₄ alkyl and C₁₋₄ alkyl-sulfonyl, (9) acarbamoyl group which may be substituted by C₁₋₆ alkyl(s), (10) formyl,(11) a C₂₋₆ alkanoyl group, (12) a C₆₋₁₄ aryl group, (13) a C₆₋₁₄aryl-carbonyl, (14) a C₇₋₁₃ aralkyl-carbonyl, (15) a hydroxyl group,(16) a C₂₋₅ alkanoyl-oxy, (17) a C₇₋₁₃ aralkyl-carbonyloxy (18) a nitrogroup, (19) a sulfamoyl group, (20) a N—C₁₋₄ alkyl-sulfamoyl, (21) aphenyl-thio, (22) a C₁₋₄ alkyl-phenylthio, (23) —N═N-phenyl, (24) acyano group, (25) an oxo group, (26) an amidino group, (27) a carboxylgroup, (28) a C₁₋₄ alkoxy-carbonyl group, (29) a C₁₋₆ alkyl-thio, (30) aC₁₋₆ alkyl-sulfinyl, (31) a C₁₋₆ alkyl-sulfonyl, (32) a C₆₋₁₄ aryl-thio,(33) a C₆₋₁₄ aryl-sulfinyl, (34) a C₆₋₁₄ aryl-sulfonyl and (35) aheterocyclic group selected from Group a6

Group a15

a C₁₋₆ alkyl group, a C₁₋₆ alkanoyl, a C₇₋₁₃ aryl-carbonyl, a C₁₋₆alkyl-sulfonyl, an aminosulfonyl, a mono-C₁₋₆ alkyl-aminosulfonyl, adi-C₁₋₆ alkyl-aminosulfonyl and a C₁₋₄ alkyl group substituted byhalogen

Group a16

(1) an aromatic heterocyclic group selected from Groups 24 and 26, and(2) a saturated or unsaturated non-aromatic heterocyclic group selectedfrom Group a25, each of which contains at least one hetero atom of oneto three hetero atoms selected from the group consisting of an oxygenatom, a sulfur atom and a nitrogen atom as ring constituting atom(s) (aring atom)

Group a17

(1) a C₁₋₆ alkyl group which may be substituted by halogen or a C₁₋₆alkoxy, (2) a C₆₋₁₂ aryl group, (3) a C₆₋₁₂ aryl group substituted byC₁₋₄ alkyl(s), (4) a C₃₋₈ cycloalkyl group which may be substituted byhalogen(s) or C₁₋₆ alkoxy(s), (5) a C₁₋₆ alkoxy group, (6) a C₁₋₆alkanoyl, (7) a C₇₋₁₃ aryl-carbonyl, (8) a C₇₋₁₃ aryl-carbonylsubstituted by C₁₋₄ alkyl(s), (9) a C₁₋₆ alkyl-sulfonyl, (10) a C₆₋₁₄aryl-sulfonyl, (11) a aminosulfonyl, (12) a mono- or di-substitutedaminosulfonyl substituted by C₁₋₄ alkyl(s) and (13) a C₁₋₆alkoxy-carbonyl which may be substituted by halogen(s)

Group a18

(1) a hydroxyl group, (2) an amino group, (3) a mono or di-substitutedamino group substituted by member(s) selected from Group a28, (4) ahalogen atom, (5) a nitro group, (6) a cyano group, (7) a C₁₋₆ alkylgroup which may be substituted by halogen atom(s) and (8) a C₁₋₆ alkoxygroup which may be substituted by halogen atom(s)

Group a19

a C₁₋₆ alkyl group which may be substituted by member(s) selected fromGroup a18, a C₃₋₆ cycloalkyl group which may be substituted by member(s)selected from Group a18, a C₆₋₁₀ aryl group which may be substituted bymember(s) selected from Group a18, a C₇₋₁₀ aralkyl group which may besubstituted by member(s) selected from Group a18, a C₁₋₆ alkoxy groupwhich may be substituted by member(s) selected from Group a18 and aheterocyclic group selected from Group a16 which may be substituted bymember(s) selected from Group a18

Group a20

a C₁₋₆ alkyl group, a C₃₋₆ cycloalkyl group and a C₇₋₁₀ aralkyl group

Group a21

a 1-azetidinyl-carbonyl, a 1-pyrrolidinyl-carbonyl, a1-piperidinyl-carbonyl, a 4-morpholinyl-carbonyl and a1-piperazinyl-carbonyl which may be substituted by member(s) selectedfrom Group a27

Group a22

a C₁₋₁₀ alkyl-sulfonyl which may be substituted by member(s) selectedfrom Group a18, a C₂₋₆ alkenyl-sulfonyl which may be substituted bymember(s) selected from Group a18, a C₂₋₆ alkynyl-sulfonyl which may besubstituted by member(s) selected from Group a18, a C₃₋₉cycloalkyl-sulfonyl which may be substituted by member(s) selected fromGroup a18, a C₃₋₉ cycloalkenyl-sulfonyl which may be substituted bymember(s) selected from Group a18, a C₆₋₁₄ aryl-sulfonyl which may besubstituted by member(s) selected from Group a18 and a C₇₋₁₀aralkyl-sulfonyl group which may be substituted by member(s) selectedfrom Group a18

Group a23

a C₁₋₆ alkoxy group, a halogen atom, a C₁₋₆ alkyl group, an amino group,a hydroxyl group, a cyano group and an amidino group

Group a24

furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl

Group a25

oxylanyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl, tetrahydropyranyl, morpholinyl,thiomorpholinyl and piperazinyl

Group a26

benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl,1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzisoxazolyl,benzothiazolyl, benzopyranyl, 1,2-benzisothiazolyl, benzodioxolyl,benzimidazolyl, 2,1,1-benzoxadiazolyl, 1H-benzotriazolyl, quinolyl,isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl,naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl,β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl,phenazinyl, phenoxathiinyl, thianthrenyl, phenanthridinyl,phenathrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl,pyrazolo[1,5-a]pyridyl, pyrazolo[3,4-b]pyridyl, imidazo[1,2-a]pyridyl,imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl,imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl and1,2,4-triazolo[4,3-b]pyridazinyl

Group a27

a C₁₋₆ alkyl group, a C₇₋₁₀ aralkyl group and a C₆₋₁₀ aryl group

Group a28

a C₁₋₆ alkyl group, a C₁₋₆ alkanoyl, a C₇₋₁₃ aryl-carbonyl and a C₁₋₆alkyl-sulfonyl

(I-2) a compound as shown in the above (1-1), wherein the 3- to8-membered saturated or unsaturated nonaromatic heterocyclic group whichmay be substituted by member(s) selected from Group a1, represented byeach of R^(a1) and R^(a2) is a 3- to 8-membered saturated or unsaturatednonaromatic heterocyclic group selected from Group a25 which may besubstituted by member(s) selected from Group a1, and the heterocyclicgroup, selected from Group a4 which may be substituted by member(s)selected from Group a3 formed by combining R^(a1) and R^(a2) togetherwith A^(a) is a cyclic-amino group selected from Group a29 which may besubstituted by member(s) selected from Group a3.

Group a29

1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 1-homopiperidinyl,heptamethylenimino, 1-piperazinyl, 1-homopiperazinyl, 4-morpholinyl,4-thiomorpholinyl, 2-isoindolinyl, 1,2,3,4-tetrahydro-2-isoquinolyl,1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl andindene-1-spiro-4′-piperidine-1′-yl

(I-3) a compound as shown in the above (I-1) wherein R^(a1) and R^(a2)combine each other together with A^(a) to form a 3-to 8-memberedsaturated or unsaturated non-aromatic heterocyclic group selected fromGroup a4, which may be substituted by member(s) selected from Group a3.

(I-4) a compound as shown in the above (1-1) wherein R^(a1) and R^(a2)combine each other together with Aa to form a 3- to 8-membered saturatedor unsaturated non-aromatic heterocyclic group containing one or twonitrogen atoms, which ring may be substituted by member(s) selected fromGroup a3.

(I-5) a compound as shown in the above (I-3), wherein the grouprepresented by -A^(a)R^(a1)R^(a2) is (1) a piperidinyl or (2) apiperazinyl group, each of which may be substituted by member(s)selected from Group a3.

(I-6) a compound as shown in the above (I-3), wherein the grouprepresented by -A^(a)R^(a1)R^(a2) is a group represented by the formula:

[wherein L^(a) is methine or a nitrogen atom, B^(a2) is a bond, —CH₂—,—SO₂—, —SO—, —S—, —O—, —CO—, —NR^(ab1)—SO₂— (wherein R^(ab1) is ahydrogen atom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynylgroup, a C₃₋₆ cycloalkyl group), —CH(OH)—, —NR^(ab2)— (wherein R^(ab2)is a hydrogen atom or a C₂₋₄ alkanoyl group), —NR^(ab1)—CO— (whereinR^(ab1) has the same meaning given above), —NR^(ab1)—CO—O— (whereinR^(ab1) has the same meaning given above), —CH₂SO₂— or —CH₂S—, R^(aa) isa hydrocarbon group selected from Group a2 which may be substituted bymember(s) selected from Group a1 or a heterocyclic group selected fromGroup a6 which may be substituted by member(s) selected from Group a1].

(I-7) a compound as shown in the above (I-3), wherein the grouprepresented by the formula -A^(a)R^(a1)R^(a2) is a group represented bythe formula:

(wherein B^(a3) is —CH₂—, —SO₂—, —SO—, —S—, —O—, —CO—, —NR^(ab1)—SO₂—(wherein R^(ab1) is a hydrogen atom, a C₁₋₄ alkyl group, a C₂₋₆ alkenylgroup, a C₂₋₆ alkynyl or a C₃₋₆ cycloalkyl group), —NR^(ab1)—CO—,—NR^(ab1)—CO—O— (wherein R^(ab1) has the same meaning given above),Z^(a) is a halogen, SO₂NR^(ab3)R^(ab4) (wherein each of R^(ab3) andR^(ab4) is (1) a C₁₋₆ alkyl which may be substituted by halogen(s),hydroxyl(s) or C₁₋₆ alkoxy(s), (2) a C₃₋₈ cycloalkyl which may besubstituted by halogen(s) or C₁₋₆ alkoxy(s), (3) a C₁₋₆ alkoxy or (4) ahydrogen atom or, R^(ab3) and R^(ab4) are combine each other togetherwith nitrogen to form a cyclic-amino group), SO₂R^(ab5), (whereinR^(ab5) is (1) a C₁₋₆ alkyl group which may be substituted byhalogen(s), hydroxyl(s) or C₁₋₆ alkoxy(s), (2) a C₃₋₈ cycloalkyl groupwhich may be substituted by halogen(s) or C₁₋₆ alkoxy(s)), aCONR^(ab3)R^(ab4) (wherein each of R^(ab3) and R^(ab4) has the meaninggiven above) or —NR^(ab7)—SO₂R^(ab6) (wherein R^(ab6) is (1) a C₁₋₆alkyl group which may be substituted by halogen(s) or C₁₋₆ alkoxy(s),(2) a C₃₋₈ cycloalkyl group which may be substituted by halogen(s) orC₁₋₆ alkoxy(s), R^(ab7) is (1) a C₁₋₆ alkyl group which may besubstituted by halogen(s) or C₁₋₆ alkoxy(s), (2) a C₃₋₈ cycloalkyl groupwhich may be substituted by halogen(s) or C₁₋₆ alkoxy(s) or (3) ahydrogen atom), a C₁₋₆ alkoxy group, an amino group which may besubstituted by C₂₋₄ alkanoyl(s), nitro(s), cyano(s), tetrazolyl(s) ormorpholinyl(s)).

(I-8) a compound as shown in the above (1-1), wherein R^(a3) is a C₆₋₁₄aryl group which may be substituted by member(s) selected from Group a1.

(I-9) a compound as shown in the above (I-1), wherein R^(a3) is a phenylgroup which may be substituted by member(s) selected from Group a1.

(I-10) a compound, wherein E^(a) is —CH₂CH₂—, —CH₂CH₂CH₂—,—CH₂CH₂CH₂CH₂— or —CH₂CH₂CH₂CH₂CH₂—.

(I-11) a compound, wherein E^(a) is —CH₂CH₂CH₂—.

(I-12) a compound, wherein G^(a2) is CO, SO₂, CONH or OCO.

(I-13) a compound, wherein G^(a2) is CO or NHCO.

(I-14) a compound, wherein G^(a2) is CO.

(I-15) a compound, wherein J^(a) is methine.

(I-16) a compound, wherein G^(a1) is CO or SO₂.

(I-17) a compound as shown in the above (I-1), wherein R^(a4) is ahydrocarbon group selected from Group a2 which may be substituted bymember(s) selected from Group a1, a heterocyclic group selected fromGroup a6 which may be substituted by member(s) selected from Group a1, aC₁₋₆ alkoxy group which may be substituted by member(s) selected fromGroup a7, or an amino group which may be substituted by member(s)selected from Group a9.

(I-18) a compound, wherein R^(a4) is a C₁₋₃ alkyl.

(I-19) a compound, wherein R^(a4) is methyl.

(I-20) a compound, wherein each of Q^(a) and R^(a) is —CH₂CH₂—.

(I-21) a compound, wherein na is zero.

(I-22) a compound represented by the formula:

[wherein R^(a4a) is (1) a C₁₋₆ alkyl group which may be substituted byhalogen(s), C₁₋₆ alkoxy(s), oxo(s), amino(s), phenyl(s), pyridyl(s) ortetrazolyl(s), (2) a C₁₋₆ alkenyl group, (3) a C₃₋₈ cycloalkyl groupwhich may be substituted by halogen(s), C₁₋₆ alkyl(s) or C₁₋₆ alkoxy(s),(4) a phenyl group which may be substituted by halogen(s), C₁₋₆alkyl(s), C₁₋₆ alkoxy(s), nitro(s), cyano(s), hydroxyl(s), C₁₋₄alkanoyl-amino(s), carbamoyl(s) or sulfamoyl(s), (5) an amino groupwhich may be substituted by C₁₋₆ alkyl(s), (6) a C₁₋₆ alkoxy group whichmay be substituted by phenyl(s), (7) a C₃₋₈ cycloalkyl-oxy group (8) aheterocyclic group which may be substituted by halogen(s), C₁₋₆ alkyl(s)or hydroxyl (s), G^(a1a) is CO or SO₂, R^(a3)a is a C₆₋₁₀ aryl groupwhich may be substituted by (1) halogen(s), (2) C₁₋₆ alkyl(s) which maybe substituted by halogen(s), (3) C₁₋₆ alkoxy(s) which may besubstituted by halogen(s), (4) C₁₋₆ alkyl-thio(s), or (5) C6-10 arylgroup which may be substituted by C₁₋₆ alkyl-sulfonyl(s), La is methineor a nitrogen atom, B^(a2) is a bond, —CH₂—, —SO₂—, —SO—, —S—, —O—,—CO—, —NR^(ab1)—SO₂— (wherein R^(ab1) has the same meaning given above),—CH(OH)—, —NR^(ab2)— (wherein R^(ab2) is a hydrogen atom or a C₂₋₄alkanoyl group), —NR^(ab1)—CO——O— (wherein R^(ab1) has the same meaninggiven above), —NR^(ab1)—CO—O— (wherein R^(ab1) has the same meaninggiven above), —CH₂SO₂— or —CH₂S—, R^(aa,) is {circumflex over (1)} anaromatic hydrocarbon group which may be substituted by halogen(s),SO₂NR^(ab3)R^(ab4) (wherein each of R^(ab3) and R^(ab4) has the samemeaning given above), SO₂R^(ab5) (wherein R^(ab5) is (1) a C₁₋₆ alkylgroup which may be substituted by halogen(s), hydroxyl(s) or C₁₋₆alkoxy(s), (2) a C₃₋₈ cycloalkyl group which may be substituted byhalogen(s) or C₁₋₆ alkoxy(s)), CONR^(ab3)R^(ab4) (wherein R^(ab3) andR^(ab4) have the same meanings given above) or —NR^(ab7)—SO₂R^(ab6)(wherein R^(ab6) has the same meaning given above), a C₁₋₆ alkoxy, anamino which may be substituted by a C₂₋₄ alkanoyl(s), a nitro, a cyano,s tetrazolyl or a morpholinyl or {circumflex over (2)} an aromaticheterocyclic group which may be substituted by substituent(s) selectedfrom the above mentioned substituents of aromatic hydrocarbon group] orsalt thereof.

(I-23) a compound as shown in the above (I-22), wherein R^(a3a) is aphenyl group which may be substituted by halogen(s), trifluoromethyl(s)or C₁₋₆ alkyl(s).

(I-24) a compound as shown in the above (I-22), wherein L^(a) ismethine.

(I-25) a compound as shown in the above (I-22), wherein B^(a2) is —CH₂—,—SO₂—, —SO—, —S—, —O—, —CO—, —NR^(ab1)—SO₂—, —NR^(ab1)—CO— orNR^(ab1)—CO—O— (wherein R^(ab1) has the same meaning given above).

(I-26) a compound as shown in the above (1-22), wherein R^(aa), is aphenyl group which may be substituted by (1) halogen(s), (2) SO₂R^(ae)(wherein R^(ae) is a C₁₋₆ alkyl group or a C₃₋₈ cycloalkyl group), (3)N(R^(ad))SO₂Rae (wherein R^(ad) is a hydrogen atom or a C₁₋₄ alkylgroup, R^(ae) has the same meaning given above), (4) SO₂NR^(af)R^(ag)(wherein each of R^(af) and R^(ag) is a hydrogen atom or a C₁₋₆ alkylgroup or R^(af) and R^(ag) may combine each other together with anitrogen atom to form a cyclic-amino group) or (5) CONR^(af)R^(ag)(wherein R^(af) and R^(ag) are the same or different and independently ahydrogen atom or a C₁₋₆ alkyl group or, R^(af) and R^(ag) combine eachother together with a nitrogen atom to form a cyclic-amino group).

(I-27) a compound as shown in the above (I-22), wherein B² is SO₂, CH₂or N(R^(ad))—SO₂ (wherein R^(ad) is a hydrogen atom or a C₁₋₄ alkyl);R^(aa′) is a phenyl which may be substituted by (1) halogen(s), (2)SO₂R^(ae) (wherein R^(ae) is a C₁₋₆ alkyl or a C₃₋₈ cycloalkyl), (3)N(R^(ad))SO₂R^(ae) (wherein R^(ad) is a hydrogen atom or a C₁₋₄ alkyl,and R^(ae) has the same meaning given above), (4) SO₂NR^(af)R^(ag)(wherein each of R^(af) and Rag is a hydrogen atom or a C₁₋₆ alkyl orR^(af) and R^(ag) may combine each other together with a nitrogen atomto form a cyclic-amino group) or (5). CONR^(af)R^(ag) (wherein each ofR^(af) and R^(ag) is a hydrogen atom or a C₁₋₆ alkyl group or R^(af) andRag may combine each other together with a nitrogen atom to form acyclic-amino group); R^(a3a) is a phenyl group substituted by one or twomembers selected from the group of halogen atom and a C₁₋₄ alkyl.

(I-28) a compound as shown in the above (I-22), wherein G^(a1a) is SO₂or CO, L^(a) is methine, B^(a2) is SO₂ or CH₂, R^(aa), is a grouprepresented by the formula:

(wherein Z^(a) is a C₁₋₄ alkyl-sulfonyl group, a sulfamoyl group whichmay be substituted by a C₁₋₄ alkyl or a carbamoyl group); R^(a3a) is aphenyl group which may be substituted by one or two members selectedfrom the group consisting of halogen atom(s) or C₁₋₄ alkyl(s); andR^(a4a) is methyl.

Examples of the “hydrocarbon group” in the “a hydrocarbon group whichmay be substituted” represented by R^(b1) preferably include, forexample, an aliphatic chain hydrocarbon group, an alicyclic hydrocarbongroup and an aryl group etc. Examples of the aliphatic chain hydrocarbongroup include a C₁₋₆ alkyl group, for example, methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neopentyl, 1-methylpropyl, n-hexyl, isohexyl etc. Examples ofthe “alicyclic hydrocarbon group” preferably include a C₃₋₈ cycloalkylgroup such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, etc.

Examples of the aryl group preferably include a C₆₋₁₄ aryl group such asphenyl, naphthyl (1-naphthyl, 2-naphthyl), etc.

Examples of the “substituent(s)” in the “hydrocarbon group which may besubstituted” represented by R^(b1) include a hydrocarbon group which maybe substituted, a heterocyclic group which may be substituted, a halogenatom (e.g., fluorine, chlorine, bromine, iodine), a C₁₋₄ alkoxy groupwhich may be substituted, a C₁₋₄ alkylthio group which may besubstituted, a C₂₋₆ alkoxycarbonyl group which may be substituted, aC₁₋₆ alkanoyl group which may be substituted, an amino group which maybe substituted, a nitro group, a cyano group, a carbamoyl group whichmay be substituted, a sulfamoyl group which may be substituted, an acylgroup derived from a sulfonic acid, etc.

Examples of the “hydrocarbon group(s)” in the “hydrocarbon group whichmay be substituted” are those similar to the “hydrocarbon group” of the“hydrocarbon group which may be substituted”, which is represented byR^(b1). Among these substituents, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkylgroup, a C₆₋₁₄ aryl group are preferred. These examples may include thesubstituents as mentioned above for R^(b1). Examples of the“substituents” in the “hydrocarbon group which may be substituted”include, for example, a lower alkoxy group (e.g., a C₁₋₆ alkoxy groupsuch as methoxy, ethoxy, propoxy, etc.), a halogen atom (e.g., fluorine,chlorine, bromine, iodine etc.), a lower alkyl group (e.g., a C₁₋₆ alkylgroup such as methyl, ethyl, propyl, etc.), a lower alkynyl group (e.g.,a C₁₋₄ alkynyl group such as vinyl, 1-propenyl, 2-propenyl, isopropenyl,butenyl, isobutenyl, etc.), an amino group, a hydroxy group, a cyanogroup, an amidino group etc. The hydrocarbon in “hydrocarbon which maybe substituted” may have 1 to 3 substituent(s) as described above at anypossible position. Examples of the heterocyclic group in the“heterocyclic group which may be substituted” (the substituent in the“hydrocarbon group which may be substituted, which is represented byR^(b1)”) include, for example, an aromatic heterocyclic group, saturatedor unsaturated non-aromatic heterocyclic group (alicyclic heterocyclicgroup) etc., which contains at least one heteroatom(s) (preferably 1 to4 heteroatom(s), more preferably, 1 to 2 heteroatom(s)) consisting of 1to 3 kind(s) of heteroatom(s) (preferably 1 to 2 kinds of heteroatom(s))selected from an oxygen atom, a sulfur atom, a nitrogen atom, etc. asring constituting atom(s).

Examples of the “aromatic heterocyclic group” include an aromaticmonocyclic heterocyclic group such as a 5 or 6-membered aromaticmonocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl,isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, etc.); an aromatic fused heterocyclicgroup such as a 8 to 12-membered aromatic fused heterocyclic group(e.g., benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl,1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzoisooxazolyl,benzothiazolyl, benzopyranyl, 1,2-benzoisothiazolyl, 1H-benzotriazolyl,quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl,phthalazinyl, naphthylidinyl, purinyl, pteridinyl, carbazolyl,α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl,phenothiazinyl, phenazinyl, phenoxathinyl, thianthrenyl,phenanthridinyl, phenanthrolinyl, indolizinyl,pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl,imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl,imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl,1,2,4-triazolo[4,3-b]pyridazinyl, etc.); etc., preferably, aheterocyclic group consisting of the above-mentioned 5- or 6-memberedaromatic monocyclic heterocyclic group fused with a benzene ring orheterocyclic group consisting of the above-mentioned 5- or 6-memberedaromatic monocyclic heterocyclic group fused with the same or differentabove-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group,etc.

Examples of the “non-aromatic heterocyclic group” include a 3 to8-membered (preferably 5 or 6-membered) saturated or unsaturated(preferably saturated) non-aromatic heterocyclic group (aliphaticheterocyclic group) such as oxiranyl, azetidinyl, oxetanyl, thiethanyl,pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl,tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.

Examples of the “substituent(s)” of the “heterocyclic group which may besubstituted” (substituent(s) of the hydrocarbon group which may besubstituted, which is represented by R^(b1)) are those similar to the“substituent(s)” of the “hydrocarbon group which may be substituted”that is(are) the “substituent(s)” of the hydrocarbon group which may besubstituted, which is represented by R^(b1).

Examples of “C₁₋₄ alkoxy group” in the “C₁₋₄ alkoxy group which may besubstituted” include, for example, methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, isobutoxy, tert-butoxy, etc. Example of “C₁₋₄ analkylthio group” in the “C₁₋₄ an alkylthio group which may besubstituted” include, for example, methylthio, ethylthio, n-propylthio,isopropylthio, n-butylthio, isobutylthio, tert-butylthio, etc. Exampleof the “C₂₋₆ alkoxycarbonyl group” in “C₂₋₆ alkoxycarbonyl group whichmay be substituted” include, for example, methoxycarbonyl,ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,isobutoxycarbonyl, tert-butoxycarbonyl, n-pentyloxycarbonyl, etc.Examples of the “C₁₋₆ alkanoyl group” in the “C₁₋₆ alkanoyl group whichmay be substituted” include, for example, formyl, acetyl, propionyl,pivaloyl etc. Examples of the substituent in the “C₁₋₄ alkoxy groupwhich may be substituted”, “% C₁₋₄ alkylthio group which may besubstituted”, and “C₁₋₆ alkoxycarbonyl group which may be substituted”,“C₁₋₆ alkanoyl group which may be substituted” are those similar to thesubstituent(s) of the “hydrocarbon group which may be substituted”,which are the substituent(s) of the “hydrocarbon group which may besubstituted” represented by R^(b1).

Examples of the substituent(s) of the “amino group which may besubstituted” include, for example, a lower alkyl group (e.g., a C₁₋₆alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,t-butyl, pentyl, hexyl, etc.), an acyl group derived from a carboxylicacid (e.g., a C₁₋₆ alkanoyl such as formyl, acetyl, propionyl, pivaloyl,etc.), a C₇₋₁₅ arylcarbonyl such as benzoyl, etc., an acyl group derivedfrom a sulfonic acid (e.g., a C₁₋₆ alkylsulfonyl such as methylsulfonyl,ethylsulfonyl, etc.), an optionally halogenated C₂₋₆ alkoxycarbonyl(e.g., trifluoromethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl,trichloromethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, etc.), etc. Inaddition, the “amino group” in the “amino group which may besubstituted” may be substituted with an imidoyl group which may besubstituted (e.g., a C₁₋₆ alkylimidoyl, formylimidoyl, amidino, etc.),etc. Alternatively, two substituents of the amino group may form acyclic amino group together with a nitrogen atom. Examples of saidcyclic amino group include e.g. 3 to 8-membered (preferably 5 or6-membered) cyclic amino group such as 1-azetidinyl, 1-pyrrolidinyl,1-piperidinyl, 4-morpholinyl, 1-piperazinyl and 1-piperazinyl which mayhave at the 4-position a lower alkyl group (e.g., a C₁₋₆ alkyl groupsuch as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl,etc.), an aralkyl group (e.g. a C₇₋₁₀ aralkyl group such as benzyl,phenethyl, etc.), an aryl group (e.g. a C₆₋₁₀ aryl group such as phenyl,1-naphthyl, 2-naphthyl, etc.), etc.

Examples of the “carbamoyl group which may be substituted” includeunsubstituted carbamoyl, a N-mono-substituted carbamoyl group and aN,N-di-substituted carbamoyl group.

The “N-mono-substituted carbamoyl group” is a carbamoyl group having onesubstituent on the nitrogen atom and the substituent include, forexample, a lower alkyl group (e.g., a C₁₋₆ alkyl group such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,etc.), a cycloalkyl group (e.g., a C₃₋₆ cycloalkyl group such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), an aryl group(e.g., a C₆₋₁₀ aryl group such as phenyl, 1-naphthyl, 2-naphthyl, etc.),an aralkyl group (e.g., a C₇₋₁₀ aralkyl group, preferably a phenyl-C₁₋₄alkyl group such as benzyl, phenethyl, etc.), a heterocyclic group(e.g., the above described “heterocyclic group” as the substituent ofthe “hydrocarbon group which may be substituted” represented by R^(b1),etc.), etc. The lower alkyl group, the cycloalkyl group, the aryl group,the aralkyl group and the heterocyclic group as described above may havesubstituent(s), and the substituent(s) include, for example, a hydroxygroup, an amino group which may be substituted [the amino group may have1 or 2 substituent(s) (e.g. a lower alkyl group (e.g., a C₁₋₆ alkylgroup such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,t-butyl, pentyl, hexyl, etc.), an acyl group (e.g., a C₁₋₆ alkanoyl suchas formyl, acetyl, propionyl, pivaloyl, etc., an arylcarbonyl such asbenzoyl, etc., a C₁₋₆ alkylsulfonyl such as methylsulfonyl,ethylsulfonyl, etc.), etc.)], a halogen atom (e.g., fluorine, chlorine,bromine, iodine, etc.), a nitro group, a cyano group, a lower alkylgroup which may be substituted with 1 to 5 halogen atom(s) (e.g.,fluorine, chlorine, bromine, iodine, etc.), a lower alkoxy group whichmay be substituted with 1 to 5 halogen atom(s) (e.g., fluorine,chlorine, bromine, iodine, etc.), etc. The lower alkyl group includes,e.g. a C₁₋₆ alkyl group such as methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, etc. and inparticular methyl, ethyl, etc. are preferable. Said lower alkoxy groupinclude e.g. a C₁₋₆ alkoxy group such as methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc. and inparticular methoxy, ethoxy, etc. are preferable. The above describedlower alkyl group, cycloalkyl group, aryl group, aralkyl group andheterocyclic group may have 1, 2 or 3 (preferably 1 or 2)substituent(s).

The “N,N-di-substituted carbamoyl group” is a carbamoyl group having twosubstituents on the nitrogen atom. Examples of one of the substituentsinclude the same as those of the above described “N-mono-substitutedcarbamoyl group” and examples of the other substituent include e.g. alower alkyl group (e.g., a C₁₋₆ alkyl group such as methyl, ethyl,propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), a C₃₋₆cycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, etc.), a C₇₋₁₀ aralkyl group (e.g., benzyl, phenethyl, etc.,preferably phenyl-C₁₋₄ alkyl group, etc.), etc. In addition, twosubstituents of the “N,N-di-substituted carbamoyl group” may form acyclic amino group together with a nitrogen atom. Examples of saidcyclic aminocarbonyl group include, e.g., 3 to 8-membered (preferably 5or 6-membered) cyclic aminocarbonyl group such as 1-azetidinylcarbonyl,1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 4-morpholinylcarbonyl,1-piperazinylcarbonyl and 1-piperazinylcarbonyl which may have a loweralkyl group (e.g., a C₁₋₆ alkyl group such as methyl, ethyl, propyl,isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), an aralkyl group (e.g.,a C₇₋₁₀ aralkyl group such as benzyl, phenethyl, etc.), an aryl group(e.g., a C₆₋₁₀ aryl group such as phenyl, 1-naphthyl, 2-naphthyl, etc.),etc. at the 4-position.

Examples of the “sulfamoyl group which may be substituted” include anunsubstituted sulfamoyl group, a N-mono-substituted sulfamoyl group anda N,N-di-substituted sulfamoyl group.

The “N-mono-substituted sulfamoyl group” is a sulfamoyl group having onesubstituent at the nitrogen atom, and examples of the substituentinclude those mentioned for the substituents of N-mono-substitutedcarbamoyl group. The “N,N-di-substituted sulfamoyl group” is a sulfamoylgroup having two substituents at the nitrogen atom, and examples of thesubstituents include those mentioned as the substituents of theN,N-di-substituted carbamoyl group. Examples of the “acyl group derivedfrom a sulfonic acid” include a sulfonyl group substituted by ahydrocarbon group, and preferably, include an acyl group such as C₁₋₁₀alkylsulfonyl, C₂₋₆ alkenylsulfonyl, C₂₋₆ alkynylsulfonyl, C₃₋₉cycloalkylsulfonyl, C₃₋₉ cycloalkenylsulfonyl, C₆₋₁₄ arylsulfonyl, C₇₋₁₀aralkylsulfonyl. Examples of the C₁₋₁₀ alkyl include, for example,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,hexyl, heptyl, octyl, etc. Examples of the C₂₋₆ alkenyl include, forexample, vinyl, allyl, 1-propenyl, isopropenyl, 2-butenyl, 3-butenyl,2-hexenyl, etc. Examples of C₂₋₆ alkynyl include, for example, ethynyl,2-propynyl, 2-butynyl, 5-hexynyl, etc.

Examples of the C₃₋₉ cycloalkyl include, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc. Examples of theC₃₋₉ cycloalkenyl include, for example, 1-cyclopenten-1-yl,2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 3-cyclohexen-1-yl,3-cycloocten-1-yl, etc. Examples of the C₆₋₁₄ aryl include, for example,phenyl, 1-naphthyl, 2-naphthyl, etc. Examples of the C₇₋₁₀aralkylsulfonyl include, for example, benzyl, phenethyl, etc. Thesehydrocarbon groups which are the substituents of the sulfonyl may besubstituted. Examples of these substituents include, for example,hydroxy group, amino group which may be substituted [the amino group maybe substituted by one or two lower alkyl group (e.g., C₁₋₆ alkyl such asmethyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,hexyl, etc.), an acyl group (e.g., a C₁₋₆ alkanoyl such as formyl,acetyl, propionyl, pivaloyl, etc., an aryl carbonyl such as benzoyl,etc., a C₁₋₆ alkylsulfonyl such as methylsulfonyl, ethylsulfonyl,etc.)], a halogen atom (for example, fluorine, chlorine, bromine,iodine, etc.), nitro group, cyano group, a lower alkyl which may besubstituted by 1 to 5 halogen atom(s) (e.g. fluorine, chlorine, bromine,iodine, etc.), a lower alkoxy group which may be substituted by 1 to 5halogen atom(s) (e.g. fluorine, chlorine, bromine, iodine, etc.).Examples of the lower alkyl group include, for example, a C₁₋₆ alkylgroup such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, pentyl, hexyl, etc., and preferably includemethyl, ethyl, etc. The lower alkoxy group includes, for example, a C₁₋₆alkoxy group such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec-butoxy, tert-butoxy, etc, and preferably include methoxy,ethoxy, etc. Preferably, one, two or three (preferably one or two) fromthese substituents are used, wherein the substituents may be the same ordifferent. “Cyclic hydrocarbon group” in the “cyclic hydrocarbon groupwhich may be substituted” represented by R^(b2) include alicyclichydrocarbon group and aryl group.

Examples of the “alicyclic hydrocarbon group” include, for example, asaturated or unsaturated alicyclic hydrocarbon group such as acycloalkyl group, a cycloalkenyl group, a cycloalkanedienyl group, etc.Examples of the “cycloalkyl group” include, for example, a C₃₋₉cycloalkyl (preferably, a C₃₋₈ cycloalkyl etc.) such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclononyl, etc., and a fused ring such as 1-indanyl, 2-indanyl, etc.Examples of the “cycloalkenyl group” include, for example, a C₃₋₆cycloalkenyl group such as 2-cyclopenten-1-yl, 3-cyclopenten-1-yl,2-cyclohexen-1-yl, 3-cyclohexen-1-yl, 1-cyclobuten-1-yl,1-cyclopenten-1-yl, etc. Examples of the “cycloalkanedienyl group”include, for example, a C₄₋₆ cycloalkanedienyl group such as2,4-cyclopentanedien-1-yl, 2,4-cyclohexanedien-1-yl,2,5-cyclohexanedien-1-yl, etc. In particular, a C₃₋₈ cyrloalkyl groupsuch as cyclohexyl is preferable.

Examples of the “aryl group” include, for example, a monocyclic or fusedpolycyclic aromatic hydrocarbon group. Among others, a C₆₋₁₄ aryl groupsuch as phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl,4-indanyl, 5-indanyl, etc. are preferable. In particular, phenyl,1-naphthyl, 2-naphthyl, etc. are preferable.

Examples of the “substituent(s)” in the “cyclic hydrocarbon group whichmay be substituted” represented by R^(b2) are those similar to the“substituent” of the “hydrocarbon group which may be substituted”described as the substituent(s) of the “hydrocarbon group which may besubstituted”, which are represented by R^(b1).

Examples of the “heterocyclic group which may be substituted” of R^(b2)are those similar to the “heterocyclic group which may be substituted”described as the substituent(s) of the “hydrocarbon group which may besubstituted”, which are represented by R^(b1).

The halogen atom represented by R^(b3) include, for example, fluorine,chlorine, bromine, iodine, etc.

The “carbamoyl group which may be substituted”, “sulfamoyl group whichmay be substituted” and “acyl group derived from a sulfonic acid”represented by R^(b3) are those similar to the “carbamoyl group whichmay be substituted”, “sulfamoyl group which may be substituted” and“acyl group derived from a sulfonic acid”, which are represented by RbExamples of the “C₁₋₄ alkyl group” of the “C₁₋₄ alkyl group which may besubstituted” represented by R^(b3) include, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl. Examples of the“C₁₋₄ alkoxy group”of the “C₁₋₄ alkoxy group which may be substituted”represented R^(b3) include, for example, methoxy, ethoxy, propoxy,n-butoxy, isobutoxy, tert-butoxy.

Example of the substituent(s) in the “C₁₋₄ alkyl group which may besubstituted” and “C₁₋₄ alkoxy group which may be substituted”, which isrepresented by R^(b3) are those similar to the “substituent(s)” of the“hydrocarbon group which may be substituted” which is(are) the“substituent(s)” of “the hydrocarbon group which may be substituted”,which is represented by R^(b1).

Examples of the substituents of “amino group which may be substituted”represented by R^(b3) include, for example, a lower alkyl group (e.g.,C₁₋₆ alkyl group such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group derived fromcarboxylic acid (e.g., C₁₋₆ alkanoyl such as formyl, acetyl, propionyl,pivaloyl, etc.), for example, C₇₋₁₅ arylcarbonyl such as benzoyl, etc,an acyl group derived from sulfonic acid (e.g., C₁₋₆ alkylsulfonyl suchas methylsulfonyl, ethylsulfonyl, etc.), an optionally halogenated C₁₋₆alkoxycarbonyl (e.g., trifluoromethoxycarbonyl,2,2,2-trifluoroethoxycarbonyl, trichloromethoxycarbonyl,2,2,2-trichloroethoxycarbonyl, etc.), etc. In addition, the “aminogroup” of the “amino group which may be substituted” may be substitutedwith an imidoyl group which may be substituted (e.g., a C₁₋₆alkylimidoyl, formylimidoyl, amidino, etc.), etc. and two substituentsof the “amino group” may form a cyclic amino group together with anitrogen atom. Examples of said cyclic amino group include, for example,3 to 8-membered (preferably, 5 or 6-membered) cyclic amino group such as1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl,1-piperazinyl and 1-piperazinyl which may have a lower alkyl group(e.g., a C₁₋₆ alkyl group such as methyl, ethyl, propyl, isopropyl,butyl, t-butyl, pentyl, hexyl, etc.), an aralkyl group (e.g., a C₇₋₁₀aralkyl group such as benzyl, phenethyl, etc.), an aryl group (e.g., aC₆₋₁₀ aryl group such as phenyl, 1-naphthyl, 2-naphthyl, etc.), etc. atthe 4-position. Examples of the leaving group represented by X include,for example, a halogen atom (e.g., a chlorine atom, a bromine atom, aniodine atom, etc.), an alkyl or aryl sulfonyloxy group (e.g.,methanesulfonyloxy, trifluoromethanesulfonyloxy, ethanesulfonyloxy,benzenesulfonyloxy, p-toluenesulfonyloxy, etc.), etc.

Examples of the salt of a compound of the formula (II) of the presentinvention include a salt with an acid, for example, a salt withinorganic acid (e.g., hydrochloric acid salt, sulfuric acid salt,hydrobromic acid salt, phosphoric acid salt, etc.), a salt of an organicacid (e.g., acetic acid salt, trifluoroacetic acid salt, succinic acidsalt, maleic acid salt, fumaric acid salt, propionic acid salt, citricacid salt, tartaric acid salt, lactic acid salt, oxalic acid salt,methanesulfonic acid salt, p-toluenesulfonic acid salt, etc.), etc., asalt with a base (e.g., an alkali metal salt such as potassium salt,sodium salt, lithium salt, etc., an alkaline earth metal salt such ascalcium salt, magnesium salt, etc., ammonium salt, a salt with anorganic base such as ammonium salt, trimethylamine salt, triethylaminesalt, tert-butyl dimethyl amine salt, dibenzyl methylamine salt, benzyldimethylamine salt, N,N-dimethylaniline salt, pyridine salt, quinolinesalt, etc.).

The compound of the formula (II) or salt thereof may also be hydrated.Hereinafter the compound of the formula (II), its salt and its hydrateare referred to as Compound (II).

Among the compounds represented by the formula (II) or salts thereof(hereinafter referred to as Compounds (II)), the following compounds arepreferable.

(II-1) the compound wherein R^(b3) is a halogen atom, a C₁₋₄ alkyl groupwhich may be substituted, a C₁₋₄ alkoxy group which may be substituted,an amino group which may be substituted, a nitro group or a cyano group,

(II-2) the compound wherein R^(b1) is an alicyclic hydrocarbon groupwhich may be substituted or an aryl group which may be substituted,

(II-3) the compound wherein R^(b1) is a hydrocarbon group which may besubstituted by 1 to 4 substituent(s) selected from 1) a hydrocarbongroup which may be substituted, 2) an heterocyclic group which may besubstituted, 3) a C₁₋₄ alkoxy group which may be substituted, 4) a C₁₋₄alkylthio group which may be substituted, 5) a C₂₋₆ alkoxycarbonyl groupwhich may be substituted, 6) a C₁₋₆ alkanoyl group which may besubstituted, 7) an amino group which may be substituted, 8) a cyclicamino group, 9) a halogen atom, 10) a nitro group, 11) a cyano group,12) a carbamoyl group which may be substituted, 13) a sulfamoyl groupwhich may be substituted and 14) an acyl group derived from a sulfonicacid,

(II-4) the compound wherein R^(b1) is a hydrocarbon group which may besubstituted by 1 to 4 substituent(s) selected from 1) a hydrocarbongroup which may be substituted, 2) a heterocyclic group which may besubstituted, 3) a C₁₋₄ alkoxy group which may be substituted, 4) a C₁₋₄alkylthio group which may be substituted, 5) a C₂₋₆ alkoxycarbonyl groupwhich may be substituted, 6) an amino group which may be substituted, 7)a halogen atom, 8) a nitro group and 9) a cyano group,

(II-5) the compound wherein R^(b1) is a hydrocarbon group which may besubstituted by 1 to 4 substituent(s) selected from 1) a hydrocarbongroup which may be substituted, 2) a heterocyclic group which may besubstituted, 3) a C₁₋₄ alkylthio group which may be substituted, 4) aC₂₋₆ alkoxycarbonyl group which may be substituted, 5) an amino groupwhich may be substituted, 6) a halogen atom and 7) a nitro group,

(II-6) the compound wherein R^(b2) is an cyclic hydrocarbon group whichmay be substituted,

(II-7) the compound wherein R^(b3) is a halogen, a carbamoyl group whichmay be substituted, a sulfamoyl group which may be substituted or anacyl group derived from a sulfonic acid,

(II-8) the compound wherein R^(b3) is a halogen,

(II-9) the compound wherein R^(b4) is a hydrogen atom,

(II-10) the compound wherein n is 0,

(II-11) the compound wherein R^(b1) is a hydrocarbon group selected fromGroup 3 which may be substituted by member(s) selected from Group 1;R^(b2) is a cyclic hydrocarbon group selected from Group 10 which may besubstituted by member(s) selected from Group 2, or a heterocyclic groupselected from Group 4 which may be substituted by member(s) selectedfrom Group 2; R^(b3) is a halogen atom, a carbamoyl group, aN-mono-substituted carbamoyl group which may be substituted by a memberselected from Group 11, a. N,N-di-substituted carbamoyl group which maybe substituted by a member selected from Group 11 and a member selectedfrom Group 14, a cyclic aminocarbonyl group selected from Group 17, asulfamoyl group, N-mono-substituted sulfamoyl group which may besubstituted by a member selected from Group 11, a N,N-di-substitutedsulfamoyl group which may be substituted by a member selected from Group11 and a member selected from Group 14, a cyclic aminosulfonyl groupselected from Group 20, an acyl group derived from a sulfonic acidselected from Group 15, a C₁₋₄ alkyl group which may be substituted bymember(s) selected from Group 2, a C₁₋₄ alkoxy group which may besubstituted by member(s) selected from Group 2, an amino group which maybe substituted by member(s) selected from Group 8, a cyclic amino groupselected from Group 9, a nitro group or a cyano group.

Group 1

1) a hydrocarbon group selected from Group 3 which may be substituted bymember(s) selected from Group 2, 2) a heterocyclic group selected fromGroup 4 which may be substituted by member(s) selected from Group 2, 3)a C₁₋₄ alkoxy group which may be substituted by member(s) selected fromGroup 2, 4) a C₁₋₄ alkylthio group which may be substituted by member(s)selected from Group 2, 5) a C₂₋₆ alkoxycarbonyl group which may besubstituted by member(s) selected from Group 2, 6) a C₁₋₆ alkanoylgroup, 7) an amino group which may be substituted by member(s) selectedfrom Group 8, 8) a cyclic amino group selected from Group 9, 9) ahalogen atom, 10) a nitro group, 11) a cyano group, 12) a carbamoylgroup, 13) a mono-substituted carbamoyl group which is substituted by amember selected from Group 11, 14) di-substituted carbamoyl group whichis substituted by a member selected from Group 11 and a member selectedGroup 14, 15) a cyclic amino carbamoyl group selected from Group 17, 16)a sulfamoyl group, 17) a N-mono substituted sulfamoyl group which issubstituted by a member selected from Group 11, 18) a N,N-di-substitutedsulfamoyl group which is substituted by a member selected from Group 11and a member selected Group 14, 19) an acyl group derived from asulfonic acid selected from Group 19

Group 2

1) a C₁₋₆ alkoxy group, 2) a halogen atom, 3) a C₁₋₆ alkyl group, 4) aC₁₋₄ alkynyl group, 5) an amino group, 6) a hydroxy group, 7) a cyanogroup and 8) an amidino group

Group 3

1) a C₁₋₆ alkyl group, 2) a C₃₋₈ cycloalkyl group and 3) a C₆₋₁₄ arylgroup

Group 4

1) an aromatic monocyclic heterocyclic group selected from Group 5, 2)an aromatic condensed heterocyclic group selected from Group 6 and 3) asaturated or unsaturated non-aromatic heterocyclic group selected fromGroup 7

Group 5

furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl

Group 6

benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl,1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzisoxazolyl,benzothiazolyl, benzopyranyl, 1,2-benzisothiazolyl, 1H-benzotriazolyl,quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl,phthalazinyl, naphthylidinyl, purinyl, pteridinyl, carbazolyl,α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl,phenothiazinyl, phenazinyl, phenoxathiinyl, thianthrenyl,phenanthridinyl, phenathrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl,pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl,imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl,1,2,4-triazolo[4,3-a]pyridyl and 1,2,4-triazolo[4,3-b]pyridazinyl

Group 7

oxylanyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl,tetrahydrofuryl, thiolanyl, piperidinyl, tetrahydropyranyl, morpholinyl,thiomorpholinyl and piperazinyl

Group 8

1) a C₁₋₆ alkyl, 2) a C₁₋₆ alkanoyl, 3) a C₇₋₁₃ arylcarbonyl, 4) anoptionally halogenated C₂₋₆ alkoxycarbonyl, 5) a C₁₋₆ alkylimidoyl, 6) aformylimidoyl and 7) an amidino

Group 9

1) 1-azetidinyl, 2) 1-pyrrolidinyl, 3) 1-piperidinyl, 4) 4-morpholinyl,5) 1-piperazinyl and 6) 1-piperazinyl which may have a C₁₋₆ alkyl, aC₇₋₁₀ aralkyl and a C₆₋₁₀ aryl at 4-position

Group 10

C₃₋₉ cycloalkyl, 1-indanyl, 2-indanyl, C₃₋₆ cycloalkenyl, C₄₋₆cycloalkanedienyl and C₆₋₁₄ aryl

Group 11

1) a C₁₋₆ alkyl group which may be substituted by member(s) selectedfrom Group 12, 2) a C₃₋₆ cycloalkyl group which may be substituted bymember(s) selected from Group 12, 3) a C₆₋₁₀ aryl group which may besubstituted by member(s) selected from Group 12, 4) a C₇₋₁₀ aralkylgroup which may be substituted by member(s) selected from Group 12, 5) aC₁₋₆ alkoxy group which may be substituted by member(s) selected fromGroup 12 and 6) a heterocyclic group selected from Group 13 which may besubstituted by member(s) selected from Group 12

Group 12

1) a hydroxy group, 2) an amino group, 3) an amino group which is monoor di-substituted by member(s) selected from Group 16, 4) a halogenatom, 5) a nitro group, 6) a cyano group, 7) a C₁₋₆ alkyl group whichmay be substituted by halogen atom(s) and 8) a C₁₋₆ alkoxy group whichmay be substituted by halogen atom(s)

Group 13

1) an aromatic heterocyclic group selected from Group 5 and Group 6 and2) a saturated or unsaturated non-aromatic heterocyclic group selectedfrom Group 7, each of which contains at least one heteroatom(s) selectedfrom the group consisting of an oxygen atom, a sulfur atom and anitrogen atom as ring-constituting atom(s)

Group 14

a C₁₋₆ alkyl group, a C₃₋₆ cycloalkyl group and a C₇₋₁₀ aralkyl group

Group 15

1) a C₁₋₁₀ alkylsulfonyl which may be substituted by member(s) selectedfrom Group 12, 2) a C₂₋₆ alkenylsulfonyl which may be substituted bymember(s) selected from Group 12, 3) a C₂₋₆ alkynylsulfonyl which may besubstituted by member(s) selected from Group 12, 4) a C₃₋₉cycloalkylsulfonyl which may be substituted by member(s) selected fromGroup 12, 5) a C₃₋₉ cycloalkenylsulfonyl which may be substituted bymember(s) selected from Group 12, 6) a C₆₋₁₄ arylsulfonyl which may besubstituted by member(s) selected from Group 12 and 7) a C₇₋₁₀aralkylsulfonyl which may be substituted by member(s) selected fromGroup 12

Group 16

a C₁₋₆ alkyl group, a C₁₋₆ alkanoyl, a C₇₋₁₃ arylcarbonyl and a C₁₋₆alkylsulfonyl

Group 17

1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl,4-morpholinylcarbonyl and 1-piperazinylcarbonyl which may be substitutedby member(s) selected from Group 18

Group 18

a C₁₋₆ alkyl group, a C₇₋₁₀ aralkyl group and a C₆₋₁₀ aryl group

Group 19

a C₁₋₁₀ alkylsulfonyl which may be substituted by member(s) selectedfrom Group 12, a C₂₋₆ alkenylsulfonyl which may be substituted bymember(s) selected from Group 12, a C₂₋₆ alkynylsulfonyl which may besubstituted by member(s) selected from Group 12, a C₃₋₉cycloalkylsulfonyl which may be substituted by member(s) selected fromGroup 12, a C₃₋₉ cycloalkenylsulfonyl which may be substituted bymember(s) selected from Group 12, a C₆₋₁₄ arylsulfonyl which may besubstituted by member(s) selected from Group 12, and a C₇₋₁₀aralkylsulfonyl which may be substituted by member(s) selected fromGroup 12

Group 20

1-azetidinylsulfonyl, 1-pyrrolidinylsulfonyl, 1-piperidinylsulfonyl,4-morpholinylsulfonyl and 1-piperazinylsulfonyl which may be substitutedby member(s) selected from Group 18

(II-12) the compound wherein R^(b1) is a C₃₋₈ cycloalkyl group which maybe substituted by member(s) selected from Group 1 or a C₆₋₁₄ aryl groupwhich may be substituted by member(s) selected from Group 1,

(II-13) the compound as shown in the above (II-12), wherein R^(b1) is 1)a C₆₋₁₄ aryl group which may be substituted by a halogen atom, a C₁₋₆alkyl which may be substituted by halogen(s), a C₁₋₄ alkylthio, a nitro,a carbamoyl, a sulfamoyl or a C₁₋₆ alkylsulfonyl, 2) a C₁₋₆ alkyl groupwhich may be substituted by (i) a C₂₋₆ alkoxycarbonyl group or (ii) aphenyl which may be substituted by C₁₋₆ alkyl(s) or 3) a C₃₋₈ cycloalkylgroup which may be substituted by (i) a halogen atom, (ii) a. C₁₋₆alkyl(s) which may be substituted by halogen(s) or (iii) a C₁₋₆ alkoxygroup which may be substituted by halogen(s);

-   R^(b2) is a phenyl group which may be substituted by a halogen atom,    a C₁₋₆ alkyl, a C₁₋₄ alkoxy or a cyano, a C₃₋₈ cycloalkyl group or a    pyridyl group;-   R^(b3) is (i) a halogen atom, (ii) a carbamoyl group, (iii) a    sulfamoyl group which may have one or two C₁₋₆ alkyl(s) or C₃₋₆    cycloalkyl(s) at N-atoms, a cyclic aminosulfonyl group selected from    Group 20, a C₁₋₆ alkylsulfonyl group or C₃₋₆ cycloalkylsulfonyl    group;-   R^(b4) is a hydrogen atom;-   nb is 0 or 1 and-   pb is 0 or 1,

(II-14) the compound as shown in the above (II-12), wherein R^(b1) is 1)a phenyl which may be substituted by a halogen atom, a C₁₋₃ alkyl,trifluoromethyl, methoxy, trifluoromethoxy, methylthio or nitro, 2) anaphthyl, 3) a C₁₋₆ alkyl group which may be substituted by (i) a C₂₋₃alkoxycarbonyl, (ii) phenyl or (iii) 3-isopropenylphenyl or 4)cyclohexyl group;

-   R^(b2) is a phenyl group which may be substituted by a halogen atom,    methyl, methoxy or cyano, a cyclohexyl group or a 3-pyridyl group;-   R^(b3) is (i) a halogen atom, (ii) a carbamoyl group, (iii) a    4-morpholinylsulfonyl group or (iv) a methylsulfonyl group,-   R^(b4) is a hydrogen atom;-   nb is 0 or 1; and-   pb is 0 or 1,

(II-15) the compound as shown in the above (II-12), wherein R^(b1) is aphenyl group which may be substituted by a halogen atom or a C₁₋₃ alkyl;R^(b2) is a phenyl group which may be substituted by a halogen atom andmethyl(s);

-   R^(b3) is (i) a halogen atom, (ii) a carbamoyl group, (iii) a    sulfamoyl group which may be substituted by one or two members    selected from the group consisting of C₁₋₆ alkyl and C₃₋₆ cycloalkyl    at N-atoms, (iv) a cyclic aminosulfonyl group selected from Group    20, (v) a C₁₋₆ alkylsulfonyl group or (vi) a C₃₋₆ cycloalkyl    sulfonyl group;-   R^(b4) is a hydrogen atom;-   nb is 0; and-   pb is 0 or 1.

The hydrocarbon group represented by R^(c1) includes, for example, analiphatic chain hydrocarbon group, an alicyclic hydrocarbon group, anaryl group and the like. Preferably, it is an aliphatic chainhydrocarbon group or an alicyclic hydrocarbon group.

The aliphatic chain hydrocarbon group includes, for example, a straightor branched aliphatic hydrocarbon group such as alkyl group, alkenylgroup, alkynyl group and the like, with preference given to alkyl group.Examples of the alkyl group include C₁₋₁₀ alkyl groups (preferably C₁₋₆alkyl etc.), such as methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl,1-methylpropyl, n-hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl,3,3-dimethylbutyl, 3,3-dimethylpropyl, 2-ethylbutyl, n-heptyl,1-methylheptyl, 1-ethylhexyl, n-octyl, 1-methylheptyl, nonyl and thelike Examples of the alkenyl group include C₂₋₆ alkenyl groups, such asvinyl, allyl, isopropenyl, 2-methylallyl, 1-propenyl,2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-ethyl-1-butenyl,2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl,3-hexenyl, 4-hexenyl, 5-hexenyl and the like. Examples of the alkynylgroup include C₂₋₆ alkynyl groups, such as ethynyl, 1-propynyl,2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl,3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,5-hexynyl and the like. Examples of the alicyclic hydrocarbon groupinclude saturated or unsaturated alicyclic hydrocarbon groups, such ascycloalkyl group, cycloalkenyl group, cycloalkanedienyl group and thelike, with preference given to cycloalkyl group. Examples of thecycloalkyl group include C₃₋₉ cycloalkyl (preferably C₃₋₈ cycloalkyletc.), such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, cyclononyl and the like, and fused rings suchas 1-indanyl, 2-indanyl and the like. Examples of the cycloalkenyl groupinclude C₃₋₆ cycloalkenyl groups, such as 2-cyclopenten-1-yl,3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl,1-cyclobuten-1-yl, 1-cyclopenten-1-yl and the like. Examples of thecycloalkanedienyl group include C₄₋₆ cycloalkanedienyl groups, such as2,4-cyclopentanedien-1-yl, 2,4-cyclohexanedien-1-yl,2,5-cyclohexanedien-1-yl and the like.

Examples of the aryl group include monocyclic or fused polycyclicaromatic hydrocarbon groups, which are preferably C₆₋₁₄ aryl groups,such as phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl,4-indanyl, 5-indanyl etc., and the like, with particular preferencegiven to phenyl, 1-naphthyl, 2-naphthyl and the like.

The hydrocarbon group having 2 or more carbon atoms represented byR^(c2) includes, for example, the hydrocarbon groups having 2 or morecarbon atoms among those represented by R^(c1). Of those recited withregard to R^(c1), preferred are C₂₋₆ alkyl and C₃₋₈ cycloalkyl.

When R^(c1) and R^(c2) in combination form, together with an adjacentnitrogen atom, a ring optionally having a substituent or substituents,the ring may contain, besides one nitrogen atom, a different nitrogenatom, an oxygen atom and a sulfur atom. Examples thereof includemonocyclic groups, such as 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl,1-homopiperidinyl, heptamethyleneimino, 1-piperazinyl,1-homopiperazinyl, morpholino, thiomorpholino and the like, fused ringssuch as 2-isoindolinyl, 1,2,3,4-tetrahydro-2-isoquinolyl,1,2,4,5-tetrahydro-3H-3-benzodiazepin-3-yl and the like, cyclic aminogroups such as spiro ring and the like (e.g.,indene-1-spiro-4′-piperidin-1′-yl etc.), said cyclic amino groupoptionally having 1 to 5, preferably 1 to 3, substituent(s) at achemically permitted position on the ring.

Examples of the substituent include hydroxy group, cyano group, nitrogroup, oxo group, halogen atom (e.g., fluorine atom, chlorine atom,bromine atom, iodine atom etc.), a group of the formula: —Y^(c)R^(ca)(wherein R^(ca) is a hydrocarbon group optionally having a substituentor substituents or a heterocyclic group optionally having a substituentor substituents, Y^(c) is a bond (single bond), —CR^(cb)R^(cc)—, —COO—,—CO—, —CO—NR^(cb)—, —CS—NR^(cb)—, —CO—S—, —CS—S—,—CO—NR^(cb)—CO—NR^(cc)—, —C(═NH)—NR^(cb)—, —NR^(b)—, —NR^(cb)—CO—,—NR^(cb)—CS—, —NR^(cb)—CO—NR^(cc)—, —NR^(cb)—CS—NR^(cc)—,—NR^(cb)—CO—O—, —NR^(cb)—CS—, —NR^(cb)—CO—S—, —NR^(cb)—CS—S—,—NR^(cb)—C(═NH)—NR^(cc)—, —NR^(cb)—SO₂—, —NR^(cb)—NR^(cc)—, —O—, —O—CO—,—O—CS—, —O—CO—O, —O—CO—NR^(cb)—, —O—C(═NH)—NR^(cb)—, —S—, —SO—, —SO₂—,—SO₂—NR^(cb)—, —S—CO—, —S—CS—, —S—CO—NR^(cb)—, —S—CS—NR^(cb)—,—S—C(═NH)—NR^(cb)— and the like, wherein R^(cb) and R^(cc) are each ahydrogen atom, alkyl group optionally having a substituent orsubstituents, alkenyl group optionally having a substituent orsubstituents, alkynyl group optionally having a substituent orsubstituents, an aryl group optionally having a substituent orsubstituents, cycloalkyl group or cycloalkenyl group optionally having asubstituent or substituents, a heterocyclic group optionally having asubstituent or substituents, acyl group derived from carboxylic acid,alkylsulfonyl group optionally having a substituent or substituents, anaryl sulfonyl group optionally having a substituent or substituents,etc.), and the like.

The “hydrocarbon group” of the hydrocarbon group optionally having asubstituent or substituents represented by R^(ca) include an aliphaticchain hydrocarbon group, alicyclic hydrocarbon group, aryl group and thelike. Examples of these aliphatic chain hydrocarbon group, alicyclichydrocarbon group and aryl group is the aliphatic chain hydrocarbongroup, alicyclic hydrocarbon group and aryl group represented by R^(c1)respectively. Examples of the substituent of the hydrocarbon groupinclude those mentioned as the substituents for the “hydrocarbon groupoptionally having a substituent or substituents” represented by R^(c3)to be mentioned later.

Examples of the “heterocyclic group optionally having a substituent orsubstituents” at the aforementioned R^(ca) include those mentioned asthe “heterocyclic group optionally having a substituent or substituents”represented by R^(c3) to be mentioned later.

Examples of the alkyl group optionally having a substituent orsubstituents, alkenyl group optionally having a substituent orsubstituents, alkynyl group optionally having a substituent orsubstituents, aryl group optionally having a substituent orsubstituents, cycloalkyl group or cycloalkenyl group optionally having asubstituent or substituents, heterocyclic group optionally having asubstituent or substituents, acyl group derived from carboxylic acid,alkyl sulfonyl group optionally having a substituent or substituents andarylsulfonyl group optionally having a substituent or substituents,represented by the aforementioned R^(cb) and R^(cc) include thosementioned as the substituent of the hydrocarbon group optionally havinga substituent represented by R^(c3) to be mentioned later.

It is preferable that R^(c1) and R^(c2) in combination forms, togetherwith an adjacent nitrogen atom, a heterocyclic ring optionally having asubstituent or substituents. More preferably, NR^(c1)R^(c2) is a groupof the formula:

wherein Y^(c) and R^(ca) are as defined above. As used here, Y^(c) andR^(ca) are as defined above, and R^(ca) is particularly preferably anaryl group optionally having a substituent or substituents or aheterocyclic group optionally having a substituent or substituents.

Y^(c)R^(ca) is particularly preferably a benzyl group optionally havinga substituent or substituents.

NR^(c1)R^(c2) is particularly preferably a 4-benzyl-1-piperidinyl groupoptionally having a substituent or substituents.

Examples of the hydrocarbon group of the hydrocarbon group optionallyhaving a substituent or substituents represented by R^(c3) include thosesimilar to the hydrocarbon groups represented by R^(c1), with particularpreference given to C₁₋₆ alkyl group, C₃₋₈ cycloalkyl group and arylgroup. These are exemplified by those recited for R^(c1).

The heterocyclic group of the heterocyclic group optionally having asubstituent or substituents represented by R^(c3) is, for example, anaromatic heterocyclic group, a saturated or unsaturated non-aromaticheterocyclic group (aliphatic heterocyclic group) and the like,containing, as an atom constituting the ring system, at least one(preferably 1 to 4, more preferably 1 or 2) of 1 to 3 kinds (preferably1 or 2 kinds) of the hetero atom selected from an oxygen atom, a sulfuratom, a nitrogen atom and the like. Examples of the aromaticheterocyclic group include aromatic monocyclic heterocyclic group (e.g.,5- or 6-membered aromatic monocyclic heterocyclic group such as furyl,thienyl, pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl,imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl,pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl etc.); condensedaromatic heterocyclic group [e.g., 8 to 12-membered condensed aromaticheterocyclic group (preferably a heterocycle wherein the aforementioned5- or 6-membered aromatic monocyclic heterocyclic group is condensedwith a benzene ring or a heterocycle wherein the same or different twoheterocycles of the aforementioned 5- or 6-membered aromatic monocyclicheterocyclic group are condensed), such as benzofuranyl,isobenzofuranyl, benzothienyl, indolyl, isoindolyl, 1H-indazolyl,benzindazolyl, benzooxazolyl, 1,2-benzoisooxazolyl, benzothiazolyl,benzopyranyl, 1,2-benzoisothiazolyl, 1H-benzotriazolyl, quinolyl,isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl,naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl,β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl,phenazinyl, phenoxathiinyl, thianthrenyl, phenanthridinyl,phenanthrolinyl, indolizinyl, pyrro[1,2-b]pyridazinyl,pyrrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl,imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl,1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl etc.] andthe like.

Examples of the non-aromatic heterocyclic group include 3 to 8-membered(preferably 5- or 6-membered) saturated or unsaturated (preferablysaturated) non-aromatic heterocyclic group (aliphatic heterocyclicgroup), such as oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl,tetrahydrofuryl, thioranyl, piperidinyl, tetrahydropyranyl, morpholinyl,thiomorpholinyl, piperazinyl etc., and the like.

Examples of the substituent of the hydrocarbon group optionally having asubstituent or substituents as represented by R^(c3) and the substituentof the heterocyclic group optionally having a substituent orsubstituents as represented by R^(c3) include alkyl group optionallyhaving a substituent or substituents, alkenyl group optionally having asubstituent or substituents, alkynyl group optionally having asubstituent or substituents, an aryl group optionally having asubstituent or substituents, cycloalkyl group or cycloalkenyl groupoptionally having a substituent or substituents, a heterocyclic groupoptionally having a substituent or substituents, amino group optionallyhaving a substituent or substituents, imidoyl group optionally having asubstituent or substituents, amidino group optionally having asubstituent or substituents, hydroxy group optionally having asubstituent or substituents, thiol group optionally having a substituentor substituents, optionally esterified carboxyl group, carbamoyl groupoptionally having a substituent or substituents, thiocarbamoyl groupoptionally having a substituent or substituents, sulfamoyl groupoptionally having a substituent or substituents, halogen atom (e.g.,fluorine, chlorine, bromine, iodine etc., preferably chlorine, bromineetc.), cyano group, nitro group, acyl group derived from carboxylicacid, alkyl sulfinyl group optionally having a substituent orsubstituents, alkyl sulfonyl group optionally having a substituent orsubstituents, arylsulfinyl group optionally having a substituent orsubstituents, arylsulfonyl group optionally having a substituent orsubstituents and the like, wherein 1 to 5 (preferably 1 to 3) of theseoptional substituents may be present at a substitutable position.

The aryl group of the “aryl group optionally having a substituent orsubstituents” as a substituent may be, for example, C₆₋₁₄ aryl groupsuch as phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl etc.,and the like Here, the substituent of the aryl group includes, forexample, lower alkoxy group (e.g., C₁₋₆ alkoxy group such as methoxy,ethoxy, propoxy etc., and the like), halogen atom (e.g., fluorine,chlorine, bromine, iodine etc.), lower alkyl group (e.g., C₁₋₆ alkylgroup such as methyl, ethyl, propyl etc., etc.), amino group, hydroxygroup, cyano group, amidino group and the like, wherein one or two ofthese optional substituents may be present at a substitutable position.

The cycloalkyl group of the “cycloalkyl group optionally having asubstituent or substituents” as a substituent may be, for example, C₃₋₇cycloalkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, etc., and the like. As used herein, examples ofthe substituent of the “cycloalkyl group” are similar in the kind andthe number to those exemplified for the substituent of theaforementioned “aryl group optionally having a substituent orsubstituents”.

The cycloalkenyl group of the “cycloalkenyl group optionally havingsubstituents” as a substituent may be, for example, C₃₋₆ cycloalkenylgroup such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyletc., and the like. As used herein, examples of the substituent of the“cycloalkenyl group optionally having a substituent or substituents” aresimilar in the kind and the number to those exemplified for thesubstituent of the aforementioned “aryl group optionally having asubstituent or substituents”.

The alkyl group of the “alkyl group optionally having a substituent orsubstituents” as a substituent may be, for example, C₁₋₆ alkyl such asmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, n-pentyl, isopentyl, neopentyl, 1-methylpropyl, n-hexyl,isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl,3,3-dimethylpropyl etc., and the like. As used herein, examples of thesubstituent of the alkyl group are similar in the kind and the number tothose exemplified for the substituent of the aforementioned “aryl groupoptionally having a substituent or substituents”.

The alkenyl group of the “alkenyl group optionally having a substituentor substituents” as a substituent may be, for example, C₂₋₆ alkenylgroup such as vinyl, allyl, isopropenyl, 2-methylallyl, 1-propenyl,2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-ethyl-1-butenyl,2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl,3-hexenyl, 4-hexenyl, 5-hexenyl etc., and the like. As used herein,examples of the substituent of the alkenyl group are similar in the kindand the number to those exemplified for the substituent of theaforementioned “aryl group optionally having a substituent orsubstituents”.

The alkynyl group of the “alkynyl group optionally having a substituentor substituents” as a substituent may be, for example, C₂₋₆ alkynylgroup, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl,3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl,2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl and the like. As used herein,examples of the substituent of the alkynyl group are similar in the kindand the number to those exemplified for the substituent of theaforementioned “aryl group optionally having a substituent orsubstituents”. The heterocyclic group of the “heterocyclic groupoptionally having a substituent or substituents” as a substituent maybe, for example, an aromatic heterocyclic group, a saturated orunsaturated non-aromatic heterocyclic group (aliphatic heterocyclicgroup) and the like, containing, as an atom (cyclic atom) constitutingthe ring system, at least one (preferably 1 to 4, more preferably 1 or2) of 1 to 3 kinds (preferably 1 or 2 kinds) of the hetero atom selectedfrom an oxygen atom, a sulfur atom and a nitrogen atom, and the like.

Examples of the “aromatic heterocyclic group” include aromaticmonocyclic heterocyclic group (e.g., 5- or 6-membered aromaticmonocyclic heterocyclic group, such as furyl, thienyl, pyrrolyl,oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl etc.) and condensed aromaticheterocyclic group [e.g., 8 to 12-membered condensed aromaticheterocycle (preferably a heterocycle wherein the aforementioned 5- or6-membered aromatic monocyclic heterocyclic group is condensed with abenzene ring or a heterocycle wherein the same or different twoheterocycle of the aforementioned 5- or 6-membered aromatic monocyclicheterocyclic group are condensed), such as benzofuranyl,isobenzofuranyl, benzothienyl, indolyl, isoindolyl, 1H-indazolyl,benzindazolyl, benzooxazolyl, 1,2-benzoisooxazolyl, benzothiazolyl,1,2-benzoisothiazolyl, 1H-benzotriazolyl, quinolyl, isoquinolyl,cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl,purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl,γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl,phenoxathiinyl, thianthrenyl, phenanthridinyl, phenanthrolinyl,indolizinyl, pyrro[1,2-b]pyridazinyl, pyrrazolo[1,5-a]pyridyl,imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl,imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl,1,2,4-triazolo[4,3-b]pyridazinyl etc.] and the like.

Examples of the “non-aromatic heterocyclic group”include 3 to 8-membered(preferably 5- or 6-membered) saturated or unsaturated (preferablysaturated) non-aromatic heterocyclic group (aliphatic heterocyclicgroup), such as oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl,tetrahydrofuryl, thioranyl, piperidinyl, tetrahydropyranyl, morpholinyl,thiomorpholinyl, piperazinyl etc., and the like.

The substituent that the “heterocyclic group optionally having asubstituent or substituents” as a substituent may have is exemplified bylower alkyl group (e.g., C₁₋₆ alkyl group, such as methyl, ethyl, propyletc., and the like), acyl group (e.g., C₁₋₆ alkanoyl, such as formyl,acetyl, propionyl, pivaloyl etc., benzoyl etc.), and the like.

The substituent of the “amino group optionally having a substituent orsubstituents”, “imidoyl group optionally having a substituent orsubstituents”, “amidino group optionally having a substituent orsubstituents”, “hydroxy group optionally having a substituent orsubstituents” and “thiol group optionally having a substituent orsubstituents” as a substituent may be, for example, lower alkyl group(e.g., C₁₋₆ alkyl group, such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl etc., and the like), acyl group(e.g., C₁₋₆ alkanoyl (e.g., formyl, acetyl, propionyl, pivaloyl etc.),benzoyl etc.), C₁₋₆ alkyl sulfonyl (e.g., methanesulfonyl,ethanesulfonyl etc.), C₃₋₁₄ arylsulfonyl (e.g., benzenesulfonyl,p-toluenesulfonyl etc.), optionally halogenated C₁₋₆ alkoxycarbonyl(e.g., trifluoromethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl,trichloromethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl etc.), and thelike. The “amino group” of the “amino group optionally having asubstituent or substituents” as the substituent may be substituted byimidoyl group optionally having a substituent or substituents (e.g.,C₁₋₆ alkyl imidoyl, formylimidoyl, amidino etc.), and the like. Inaddition, two substituents may form a cyclic amino group together with anitrogen atom. In this case, examples of the cyclic amino group include3 to 8-membered (preferably 5- or 6-membered) cyclic amino, such as1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, morpholino, 1-piperazinyland 1-piperazinyl optionally having, at the 4-position, lower alkylgroup (e.g., C₁₋₆ alkyl group, such as methyl, ethyl, propyl, isopropyl,butyl, t-butyl, pentyl, hexyl etc., and the like), aralkyl group (e.g.,C₇₋₁₀ aralkyl group, such as benzyl, phenethyl etc., and the like), arylgroup (e.g., C₆₋₁₀ aryl group, such as phenyl, 1-naphthyl, 2-naphthyletc., and the like), and the like.

Examples of the “carbamoyl group optionally having a substituent orsubstituents” include unsubstituted carbamoyl, N-monosubstitutedcarbamoyl group and N,N-disubstituted carbamoyl group.

The “N-monosubstituted carbamoyl group” is a carbamoyl group having onesubstituent on the nitrogen atom. Examples of the substituent includelower alkyl group (e.g., C₁₋₆ alkyl group, such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl etc., and thelike), cycloalkyl group (e.g., C₃₋₆ cycloalkyl group, such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc., and the like),aryl group (e.g., C₆₋₁₀ aryl group, such as phenyl, 1-naphthyl,2-naphthyl etc., and the like), aralkyl group (e.g., C₇₋₁₀ aralkylgroup, such as benzyl, phenethyl etc., preferably phenyl-C₁₋₄ alkylgroup etc.), heterocyclic group (e.g., those exemplified as the“heterocyclic group” as a substituent of “hydrocarbon group optionallyhaving a substituent or substituents” represented by R^(c3) and thelike). The lower alkyl group, cycloalkyl group, aryl group, aralkylgroup and heterocyclic group may have substituents, which substituentsare, for example, hydroxy group, amino group optionally having asubstituent or substituents [which amino group optionally having 1 or 2from lower alkyl group (e.g., C₁₋₆ alkyl group such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl etc., and thelike), acyl group (e.g., C₁₋₆ alkanoyl such as formyl, acetyl,propionyl, pivaloyl etc., benzoyl, etc.), and the like as substituents],halogen atom (e.g., fluorine, chlorine, bromine, iodine etc.), nitrogroup, cyano group, lower alkyl group optionally having 1 to 5 halogenatoms as substituents (e.g., fluorine, chlorine, bromine, iodine etc.)lower alkoxy group optionally having 1 to 5 halogen atoms assubstituents (e.g., fluorine, chlorine, bromine, iodine etc.), and thelike. Examples of the lower alkyl group include C₁₋₆ alkyl group, suchas methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, pentyl, hexyl etc., and the like, particularly preferablymethyl, ethyl and the like. Examples of the lower alkoxy group includeC₁₋₆ alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy,n-butoxy, isobutoxy, sec-butoxy, tert-butoxy etc., and the like,particularly preferably methoxy, ethoxy and the like. One, two or threeof these (preferably 1 or 2) are the same or different and may bepresent.

The “N,N-disubstituted carbamoyl group” is a carbamoyl group having 2substituents on a nitrogen atom. Examples of one of the substituents arethose similar to the substituents of the aforementioned“N-monosubstituted carbamoyl group” and examples of the other includelower alkyl group (e.g., C₁₋₆ alkyl group, such as methyl, ethyl,propyl, isopropyl, butyl, t-butyl, pentyl, hexyl etc., and the like),C₃₋₆ cycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl etc.), C₇₋₁₀ aralkyl group (e.g., benzyl, phenethyl etc.,preferably phenyl-C₁₋₄ alkyl group etc.) and the like. Two substituentsmay form a cyclic amino group together with a nitrogen atom. In thiscase, examples of the cyclic aminocarbamoyl group include 3 to8-membered (preferably 5- or 6-membered) cyclic amino-carbomoyl such as1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl,morpholinocarbonyl, 1-piperazinylcarbonyl and 1-piperazinylcarbonyloptionally having, at the 4-position, lower alkyl group (e.g., C₁₋₆alkyl group, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl,pentyl, hexyl etc., and the like), aralkyl group (e.g., C₇₋₁₀ aralkylgroup, such as benzyl, phenethyl etc., and the like), aryl group (e.g.,C₆₋₁₀ aryl group, such as phenyl, 1-naphthyl, 2-naphthyl etc., and thelike), and the like.

Examples of the substituent of the “thiocarbamoyl group optionallyhaving a substituent or substituents” are similar to those exemplifiedfor the substituent of the aforementioned “carbamoyl group optionallyhaving a substituent or substituents”.

Examples of the “sulfamoyl group optionally having a substituent orsubstituents” include unsubstituted sulfamoyl, N-monosubstitutedsulfamoyl group and N,N-disubstituted sulfamoyl group.

The “N-monosubstituted sulfamoyl group” means sulfamoyl group having onesubstituent on a nitrogen atom. Examples of the substituent are thosesimilar to the substituent of the “N-monosubstituted carbamoyl group”.

The “N,N-disubstituted sulfamoyl group” means sulfamoyl group having 2substituents on a nitrogen atom. Examples of the substituent are thosesimilar to the substituent of the “N,N-disubstituted carbamoyl group”.

Examples of the “optionally esterified carboxyl group” include, besidesfree carboxyl group, lower alkoxy carbonyl group, aryloxycarbonyl group,aralkyloxycarbonyl group and the like.

Examples of the “lower alkoxy carbonyl group” include C₁₋₆alkoxy-carbonyl group, such as methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl,isopentyloxycarbonyl, neopentyloxycarbonyl etc., and the like. Of these,C₁₋₃ alkoxy-carbonyl group, such as methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl etc., and the like are preferable.

Examples of the “aryloxycarbonyl group” preferably include C₇₋₁₂aryloxy-carbonyl group, such as phenoxycarbonyl, 1-naphthoxycarbonyl,2-naphthoxycarbonyl etc., and the like.

Examples of the “aralkyloxycarbonyl group” preferably include C₇₋₁₀aralkyloxy-carbonyl group (preferably C₆₋₁₀ aryl-C₁₋₄ alkoxy-carbonyletc.) such as benzyloxycarbonyl, phenethyloxycarbonyl etc., and thelike.

The “aryloxycarbonyl group” and “aralkyloxycarbonyl group” may havesubstituents. Examples of the substituent are similar in the kind andthe number to those exemplified for the substituent of aryl group andaralkyl group as the substituents of the aforementionedN-monosubstituted carbamoyl group.

The “acyl group derived from carboxylic acid” as the substituent isexemplified by one wherein a hydrogen atom or the single substituentthat the aforementioned “N-monosubstituted carbamoyl group” has on anitrogen atom is bonded to carbonyl, and the like. Preferably C₁₋₆alkanoyl such as formyl, acetyl, propionyl, pivaloyl etc. and acyl suchas venzoyl etc., and the like.

The alkyl of the “alkyl sulfinyl group optionally having a substituentor substituents” and “alkyl sulfonyl group optionally having asubstituent or substituents” as the substituent may be, for example,lower alkyl group such as C₁₋₆ alkyl group (e.g., methyl, ethyl, propyl,isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl etc.), and the like.The aryl of the “arylsulfinyl group optionally having a substituent orsubstituents” and “arylsulfonyl group optionally having a substituent orsubstituents” as the substituent may be, for example, C₆₋₁₄ aryl group,such as phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl etc.,and the like.

The substituent of these alkyl and aryl may be, for example, loweralkoxy group (e.g., C₁₋₆ alkoxy group, such as methoxy, ethoxy, propoxyetc., and the like), halogen atom (e.g., fluorine, chlorine, bromine,iodine etc.), lower alkyl group (e.g., C₁₋₆ alkyl group, such as methyl,ethyl, propyl etc., and the like), amino group, hydroxy group, cyanogroup, amidino group and the like, wherein one or two of these optionalsubstituents may be present at a substitutable position.

The hydrocarbon group optionally having a substituent or substituentsrepresented by R^(c4) is exemplified by those shown with regard tohydrocarbon group optionally having a substituent or substituentsrepresented by R^(c3), and the heterocyclic group optionally having asubstituent or substituents represented by R^(c4) is exemplified bythose shown with regard to the heterocyclic group optionally having asubstituent or substituents represented by R^(c3).

The divalent chain hydrocarbon group of the divalent chain hydrocarbongroup optionally having a substituent or substituents other than oxogroup, represented by E^(c), is exemplified by C₁₋₆ alkylene, such asmethylene, ethylene etc., C₂₋₆ alkenylene, such as ethenylene etc., C₂₋₆alkynylene, such as ethynylene etc., and the like. Preferred is C₁₋₅alkylene and more preferred is trimethylene.

The substituent of the divalent hydrocarbon group may be any as long asit is not an oxo group. Examples thereof include alkyl group optionallyhaving a substituent or substituents, an aryl group optionally having asubstituent or substituents, cycloalkyl group or cycloalkenyl groupoptionally having a substituent or substituents, optionally esterifiedcarboxyl group, carbamoyl group or thiocarbamoyl group optionally havinga substituent or substituents, amino group optionally having asubstituent or substituents, hydroxy group optionally having asubstituent or substituents, thiol (mercapto) group optionally having asubstituent or substituents, acyl group derived from carboxylic acid,alkyl sulfonyl group optionally having a substituent or substituents,arylsulfonyl group optionally having a substituent or substituents,halogen (e.g., fluorine, chlorine, bromine etc.), nitro, cyano and thelike. The number of the substituents may be 1 to 3. The alkyl groupoptionally having a substituent or substituents, the aryl groupoptionally having a substituent or substituents, the cycloalkyl group orcycloalkenyl group optionally having a substituent or substituents, theoptionally esterified carboxyl group, the carbamoyl group orthiocarbamoyl group optionally having a substituent or substituents, theamino group optionally having a substituent or substituents, the hydroxygroup optionally having a substituent or substituents, the thiol(mercapto) group optionally having a substituent or substituents, theacyl group derived from carboxylic acid, the alkyl sulfonyl groupoptionally having a substituent or substituents, the arylsulfonyl groupoptionally having a substituent or substituents are those similar to thesubstituent of the heterocyclic group optionally having a substituent orsubstituents represented by the aforementioned R^(c3).

Examples of the substituent of the methine group optionally having asubstituent or substituents represented by Jc are those similar to thesubstituent of the heterocyclic group optionally having a substituent orsubstituents represented by the aforementioned R^(c3).

The divalent chain C₁₋₃ hydrocarbon group of the divalent chain C₁₋₃hydrocarbon group optionally having a substituent or substituents,represented by Q^(c) and R^(c), is exemplified by one having 1 to 3carbon atoms from the divalent chain hydrocarbon group of the divalentchain hydrocarbon group optionally having a substituent or substituentsother than oxo group, represented by E^(c).

The substituent of the divalent chain C₁₋₃ hydrocarbon group optionallyhaving a substituent or substituents, represented by Q^(c) and R^(c), isexemplified by those exemplified as the substituent of the divalentchain hydrocarbon group optionally having a substituent or substituentsother than oxo group, represented by E^(c). The salt of the carboxylgroup or sulfonic acid group, as represented by R^(c5), is exemplifiedby salts with alkali metal, such as sodium, potassium, lithium etc.,salts with alkaline earth metal, such as calcium, magnesium, strontiumetc., ammonium salt and the like.

Among the compounds represented by the formula (III) or salts thereof(hereinafter referred to as Compound (III)), the following compounds arepreferable.

(III-1) The compound wherein R^(c1) is a C₁₋₆ alkyl group or a C₃₋₈cycloalkyl group; R^(c2) is a C₂₋₆ alkyl group or a C₃₋₈ cycloalkylgroup, or R^(c1) and R^(c2) in combination form, together with anadjacent nitrogen atom, a ring optionally having a substituent orsubstituents; R^(c3) is a C₁₋₆ alkyl group optionally having asubstituent or substituents, a C₃₋₈ cycloalkyl group optionally having asubstituent or substituents, an aryl group optionally having asubstituent or substituents or a heterocyclic group optionally having asubstituent or substituents; R^(c4) is a hydrogen atom, alkyl groupoptionally having a substituent or substituents, a C₃₋₈ cycloalkyl groupoptionally having a substituent or substituents, an aryl groupoptionally having a substituent or substituents or a heterocyclic groupoptionally having a substituent or substituents; E^(c) is a C₂₋₅alkylene group optionally having a substituent or substituents otherthan oxo group; G^(c) is CO or SO₂; J^(c) is a nitrogen atom or amethine group optionally having a substituent or substituents; and Q^(c)and R^(c) are each a bond or a C₁₋₃ alkylene group optionally having asubstituent or substituents.

(III-2) The compound wherein R^(c1) and R^(c2) in combination form,together with an adjacent nitrogen atom, a ring optionally having asubstituent or substituents.

(III-3) The compound as shown in the above (III-2), wherein the ringoptionally having a substituent or substituents is a 1-piperidinyl groupor a 1-piperazinyl group each optionally having a substituent orsubstituents.

(III-4) The compound as shown in the above (III-3), wherein thesubstituent of the 1-piperidinyl group or 1-piperazinyl group is (1)phenyl-C₁₋₄ alkyl optionally having halogen on a benzene ring, (2)diphenylmethyl optionally having hydroxy, (3) benzoyl optionally havinghalogen on a benzene ring, (4) 2-phenylethen-1-yl, (5) phenyl optionallyhaving halogen, (6) hydroxy, (7) phenoxy or (8) benzyloxy.

(III-5) The compound as shown in the above [III-2], wherein the ringoptionally having a substituent or substituents is a 1-piperidinyl groupoptionally having a substituent or substituents.

(III-6) The compound as shown in the above [III-5], wherein thesubstituent of the 1-piperidinyl group is a benzyl group optionallyhaving halogen on a benzene ring.

(III-7) The compound wherein R^(c3) is (1) a C₁₋₆ alkyl group, (2) aC₃₋₈ cycloalkyl group, (3) a benzyl group optionally having a hydroxygroup, (4) a naphthylmethyl group, (5) a phenyl group optionally having,as a substituent, (a) C₁₋₄ alkyl optionally having halogen, (b). C₁₋₄alkoxy optionally having halogen, (c) phenyl, (d) cyano, (e) benzyloxyor (f) a halogen atom, (6) a naphthyl group, (7) an indanyl group or (8)a tetrahydronaphthyl group.

(III-8) The compound wherein R^(c3) is a phenyl group optionally having,as a substituent, C₁₋₄ alkyl or halogen.

(III-9) The compound wherein E^(c) is C₂₋₆ polymethylene optionallyhaving hydroxy.

(III-10) The compound wherein R^(c4) is (1) a hydrogen atom, (2) C₁₋₆alkyl optionally having (a) halogen, (b) pyridyl, (c) morpholino, (d)furyl, (e) ethynyl or (f) C₃₋₈ cycloalkyl, (3) phenyl-C₁₋₄ alkyloptionally having (a) halogen, (b) C₁₋₄ alkyl, (c) halogeno-C₁₋₄ alkylor (d) C₁₋₄ alkoxy on a benzene ring, or (4) C₃₋₈ cycloalkyl.

(III-11) The compound wherein R^(c4) is (a) C₁₋₄ alkyl group optionallyhaving, as a substituent, halogen or furyl or (b) a benzyl groupoptionally having halogen on a benzene ring.

(III-12) The compound wherein —N(R^(c1))R^(c2) is a 1-piperidinyl groupoptionally having a substituent or substituents, E^(c) is a trimethylenegroup, R^(c3) is a phenyl group optionally having a substituent orsubstituents, G^(c) is CO, J^(c) is CH, and QC and Rc are each amethylene group. In the above formulas, examples of the C₁₋₆ alkyl groupshown by R^(da) in groups —NR^(da)—SO₂— and —NR^(da)—CO, which arerepresented by B^(d) include e.g. methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl, etc., examples of the C₂₋₆alkenyl group include e.g. vinyl, allyl, 1-propeny, isopropeny,2-butenyl, 3-butenyl, 2-hexenyl, etc., and examples of the C₃₋₈cycloalkyl group include e.g. cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cyclooctyl, etc.

Examples of the halogen atom represented by R^(d1) include e.g.fluorine,chlorine, bromine, iodine, etc., examples of the C₁₋₆ alkyl groupinclude e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,pentyl, hexyl, etc., examples of the C₂₋₄ alkenyl group include e.g.vinyl, 1-propeny, 2-propeny, isopropeny, butenyl, isobutenyl, etc.,example of C₁₋₄ alkanoyl group include e.g. formyl, acetyl, propionyl,butyryl, etc., and example of C₁₋₄ alkoxy group include e.g. methoxy,ethoxy, propoxy, etc.

Examples of halogen represented by R^(d2) include e.g. fluorine,chlorine, bromine, iodine, etc.

Examples of the C₁₋₆ alkyl in the “C₁₋₆ alkyl which may be substitutedby a halogen or C₁₋₄ alkoxy” represented by R^(d2) include e.g. methyl,ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.,examples of the halogen as the substituent includes e.g. fluorine,chlorine, bromine, iodine, etc., and examples of C₁₋₄ alkoxy as thesubstituent include e.g. methoxy, ethoxy, n-propoxy, isopropoxy,n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.

Examples of the C₁₋₄ alkoxy group in the “C₁₋₄ alkoxy which may besubstituted by a halogen or C₁₋₄ alkoxy” represented by R^(d2) includee.g. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy,sec-butoxy, tert-butoxy, etc., examples of the halogen as thesubstituent includes e.g. fluorine, chlorine, bromine, iodine, etc., andexamples of C₁₋₄ alkoxy as the substituent include e.g. methoxy, ethoxy,n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy,etc.

Examples of C₁₋₄ alkanoylamino represented by R^(d2) include e.g.formylamino, acetylamino, propionylamino, butyrylamino, etc.

In the groups SO₂NR^(db)R^(dc), CONR^(db)R^(dc) and NR^(db)R^(dc) eachof which is represented by R^(d2), examples of the “C₁₋₆ alkyl groupwhich may be substituted by a halogen or C₁₋₄ alkoxy” represented byR^(db) and R^(dc) include those mentioned for the “C₁₋₆ alkyl which maybe substituted by a halogen or C₁₋₄ alkoxy” represented by R^(d2);examples of the “C₃₋₈ cycloalkyl group which may be substituted by ahalogen or C₁₋₄ alkoxy” include e.g. cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cyclooctyl, etc.; the halogen which is thesubstituent include e.g. fluorine, chlorine, bromine, iodine, etc., andthe C₁₋₄ alkoxy which is the substituent include e.g. methoxy, ethoxy,n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy,etc.

In the groups SO₂NR^(db)R^(dc), CONR^(db)R^(dc) and NR^(db)R^(dc) eachof which is represented by R^(dc), examples of the cyclic amino groupwhich forms by combining. R^(db) and R^(dc) together with the nitrogenatom include e.g. 1) 1-azetidinyl, 2) 1-pyrrolidinyl, 3) 1-piperidinyl,4) 4-morpholinyl, 5) 1-piperazinyl and 6) 1-piperazynyl which may besubstituted by a C₁₋₆ alkyl (e.g. methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), a C₇₋₁₀ aralkyl (e.g.benzyl, phenethyl, etc) or a C₆₋₁₀ aryl (e.g. phenyl, 1-naphthyl,2-naphthyl, etc.) at 4-position. In the group NR^(da)—SO₂R^(dd)represented by R^(d2), the definition of R^(da) is the same as that ofR^(da) in groups —NR^(da)—SO₂— and —NR^(da)—CO— each of whichrepresented by B^(d).

In the groups SO₂R^(dd) and —NR^(da)—SO₂R^(dd) represented by R^(d2),examples of the C₁₋₆alkyl group represented by R^(dd) include e.g.methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,hexyl, etc. and examples of the C₃₋₈cycloalkyl group include, e.g.cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc.

In the formula (IV), (IIId) and (IVd), examples of the hydrocarbon groupin the hydrocarbon group which may be substituted represented by R^(d3)in the groups shown by the formulas (d1), (d2), (d3), (d4), (d5) and(d6) includes e.g. a C₁₋₆alkyl (e.g. methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), a C₂₋₆alkenyl (e.g.vinyl, allyl, 1-propeny, isopropeny, 2-butenyl, 3-butenyl, 2-hexenyl,etc.), a C₂₋₆alkynyl (e.g. ethynyl, 2-propynyl, 2-butynyl, 5-hexynyl,etc.), a C₃₋₈cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cyclooctyl, etc.), a C₆₋₁₀aryl (e.g. phenyl, naphthyl,etc.), etc.

Examples of the substituent of the hydrocarbon group include e.g. ahalogen (e.g. fluorine, chlorine, bromine, iodine, etc), aC₁₋₄alkoxy(e.g. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec-butoxy, tert-butoxy, etc.), phenyl, a C₁₋₆alkyl (e.g.methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, pentyl, hexyl, etc.), nitro, cyano, hydroxy, aC₁₋₄alkanoylamino (e.g. formylamino, acetylamino, propionylamino, etc.),carbamoyl, sulfamoyl, etc.

Among them, when the hydrocarbon group is a C₁₋₆alkyl, a C₂₋₆alkenyl orC₂₋₆alkynyl, preferable examples of the substituent include a halogen, aC₁₋₄alkoxy and phenyl; when the hydrocarbon group is a C₃₋₈cycloalkyl,preferable examples of the substituent include a halogen, a C₁₋₆alkyland a C₁₋₄alkoxy; when the hydrocarbon group is a C₆₋₁₀aryl, preferableexample include a halogen, a C₁₋₆alkyl, a C₁₋₄alkoxy, nitro, cyano,hydroxy, a C₁₋₄alkanoylamino, carbamoyl and sulfamoyl.

Examples of the C₁₋₄alkoxy in C₁₋₄alkoxy which may be substituentrepresented by R^(d3) include e.g. methoxy, ethoxy, propoxy, etc, andexample of the substituent in C₁₋₄alkoxy which may be substituentrepresented by R^(d3) include e.g. a halogen (e.g. fluorine, chlorine,bromine, iodine, etc.), phenyl, etc.

Examples of the amino group which may be substituted represented byR^(d3) include not only an unsubstituted amino group but also, e.g. aC₁₋₆alkylamino (e.g. methylamino, ethylamino, propylamino,isopropylamino, butylamino, isobutylamino, t-butylamino, pentylamino,hexylamino, etc.), a di(C₁₋₆alkyl)amino (e.g. dimethylamino,diethylamino, dipropylamino, dibutylamino, etc.), a C₁₋₄alkoxyamino(e.g. methoxyamino, ethoxyamino, n-propoxyamino, isopropoxyamino,n-butoxyamino, isobutoxyamino, sec-butoxyamino, tert-butoxyamino, etc.),etc.

Examples of the C₁₋₆ alkyl group represented by R^(d4) and R^(d5)include e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,pentyl, hexyl, etc.

Examples of the C₁₋₆ alkyl group represented by R^(d6) include e.g.methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,hexyl, etc. and examples of the C₂₋₆ alkenyl group include e.g. vinyl,allyl, 1-propeny, isopropeny, 2-butenyl, 3-butenyl, 2-hexenyl, etc.

Among the compounds of the formula (IV) or salts thereof (hereinafterreferred to as Compound (IV)), the following compounds are preferable.

(IV-1) a compound wherein R^(d3) is 1) C₁₋₆ alkyl group which may besubstituted by a halogen, a C₁₋₄ alkoxy or phenyl, 2) a C₂₋₆alkenylgroup, 3) a C₂₋₆alkynyl group, 4) a C₃₋₈cycloalkyl group which may besubstituted by a halogen, a C₁₋₆alkyl or a C₁₋₄alkoxy, 5) a C₆₋₁₀arylgroup which may be substituted by a halogen, a C₁₋₆alkyl, a C₁₋₄alkoxy,nitro, cyano, hydroxy, a C₁₋₄alkanoylamino, carbamoyl or sulfamoyl, 6) aC₁₋₄alkoxy group which may be substituted by a halogen or phenyl, or 7)an amino group which may be substituted by one or two groups selectedfrom the group consisting of a C₁₋₆alkyl and a C₁₋₄alkoxy;

(IV-2) a compound wherein R^(d3) is 1) C₁₋₆ alkyl group, 2) aC₂₋₆alkenyl group, 3) a C₃₋₈cycloalkyl group, 4) a C₁₋₄alkoxy group or5) an amino group which may be substituted by a C₁₋₆alkyl or aC₁₋₄alkoxy, X^(d) is —SO₂— or —CO—, nd is 1 or 2, md is 0, 1 or 2,R^(d4) and R^(d5) are the same or different, and each of which is ahydrogen atom or a methyl group, R^(d6) is a hydroxy group, methyl groupor a C₂₋₆alkenyl group, and rd is 3.

(IV-3) a compound wherein A^(d) is a group of the formula:

wherein R^(d3a) is a C₁₋₆alkyl group, X^(d1) is —SO₂— or —CO—, nd1 is 1or 2, R^(d6a) is a hydroxy group or a methyl group; rd is 3, B^(d) is—CH₂—, each of pd and qd is 0, 1 or 2, R^(d1) is a halogen atom, amethylgroup, R^(d2) is a halogen, a C₁₋₄alkoxy, nitro, aC₁₋₄alkanoylamino, SO₂NR^(db)R^(dd), SO₂R^(dd), CONR^(db)R^(dc),NR^(db)R^(dc) or NR^(da)—SO₂R^(dd) (wherein R^(da) is a hydrogen atom, aC₁₋₆alkyl group, a C₂₋₆alkenyl group or a C₃₋₈cycloalkyl group, R^(db)and R^(dc) are are the same or different, and each of which is ahydrogen atom, a C₁₋₆alkyl group or a C₃₋₈cycloalkyl group, or R^(db)and R^(dc) may combine each other together with the nitrogen atom toform a cyclic amino group, R^(dd) is a C₁₋₆alkyl group or aC₃₋₈cycloalkyl group).

“A 5- to 6-membered cyclic ring” of “a 5- to 6-membered cyclic ringgroup which may be substituted”, which is represented by R^(e1) in theabove-mentioned formula (eI), is exemplified by a group which is formedby removing one hydrogen atom from a 6-membered aromatic hydrocarbonsuch as benzene or the like, a 5- to 6-membered aliphatic hydrocarbonsuch as cyclopentane, cyclohexane, cyclopentene, cyclohexene,cyclopentadiene, cyclohexadiene or the like, a 5- to 6-membered aromaticheterocyclic ring, which contains 1 to 4 heteroatoms of 1 to 2 kindsselected from the nitrogen atom, the sulfur atom and the oxygen atom,such as furan, thiophene, pyrrole, imidazole, pyrazole, thiazole,oxazole, isothiazole, isoxazole, tetrazole, pyridine, pyrazine,pyrimidine, pyridazine, triazole or the like, a 5- to 6-membered,non-aromatic heterocyclic ring, which contains 1 to 4 heteroatoms of 1to 2 kinds selected from the nitrogen atom, the sulfur atom and theoxygen atom, such as tetrahydrofuran, tetrahydrothiophene, dithiolan,oxathiolan, pyrrolidine, pyrroline, imidazolidine, imidazoline,pyrazolidine, pyrazoline, piperidine, piperazine, oxazine, oxadiazine,thiazine, thiadiazine, morpholine, thiomorpholine, pyran,tetrahydropyran, tetrahydrothiopyran or the like, or the like, where asfor “a 5- to 6-membered cyclic ring” is preferably benzene, furan,thiophene, pyridine, cyclopentane, cyclohexane, pyrrolidine, piperidine,piperazine, morpholine, thiomorpholine, tetrahydropyran (preferably, a6-membered cyclic ring) or the like, particularly benzene.

Examples of “a substituent” which may be possessed by “a 5- to6-membered cyclic ring” of “a 5- to 6-membered cyclic ring group whichmay be substituted”, which is represented by R^(e1), to be used includea halogen atom, nitro, cyano, an alkyl which may be substituted, acycloalkyl which may be substituted, the hydroxyl group which may besubstituted, the thiol group which may be substituted (the sulfur atommay be oxidized to form a sulfinyl group which may be substituted or asulfonyl group which may be substituted), an amino group which may besubstituted, an acyl which may be substituted, the carboxyl group whichmay be esterified, an aromatic group which may be substituted and thelike.

A halogen as a substituent of R^(e1) is exemplified by fluorine,chlorine, bromine, iodine or the like, where fluorine and chlorine areparticularly preferable.

An alkyl for an alkyl which may be substituted as a substituent ofR^(e1) is exemplified by a straight-chain or branched alkyl having acarbon number of 1 to 10, for example, a C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl or thelike, preferably a lower (C₁₋₆) alkyl. A substituent in said alkyl whichmay be substituted is exemplified by a halogen (for example, fluorine,chlorine, bromine, iodine or the like), nitro, cyano, the hydroxylgroup, the thiol group which may be substituted (for example, thiol, aC₁₋₄ alkylthio or the like), an amino group which may be substituted(for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5-to 6-membered cyclic ring amino such as tetrahydropyrrole, piperazine,piperidine, morpholine, thiomorpholine, pyrrole, imidazole or the like,or the like), the carboxyl group which may be esterified or amidated(for example, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkoxylwhich may be halogenated (for example, methoxy, ethoxy, propoxy, butoxy,trifluoromethoxy, trifluoroethoxy or the like), a C₁₋₄ alkoxy-C₁₋₄alkoxyl which may be halogenated (for example, methoxymethoxy,methoxyethoxy, ethoxyethoxy, trifluoromethoxyethoxy,trifluoroethoxyethoxy or the like), formyl, a C₂₋₄ alkanoyl (forexample, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like) or the like, wherethe number of the substituents is preferably 1 to 3.

The cycloalkyl for a cycloalkyl which may be substituted as asubstituent of R^(e1) is exemplified by, for example, a C₃₋₇ cycloalkylsuch as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl orthe like. The substituent in said cycloalkyl which may be substituted isexemplified by a halogen (for example, fluorine, chlorine, bromine,iodine or the like), nitro, cyano, the hydroxyl group, the thiol groupwhich may be substituted (for example, thiol, a C₁₋₄ alkylthio or thelike), an amino group which may be substituted (for example, amino, amono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered cyclicring amino such as tetrahydropyrrole, piperazine, piperidine,morpholine, thiomorpholine, pyrrole, imidazole or the like, or thelike), the carboxyl group which may be esterified or amidated (forexample, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkoxylwhich may be halogenated (for example, methoxy, ethoxy, propoxy, butoxy,trifluoromethoxy, trifluoroethoxy or the like), a C₁₋₄ alkoxy-C₁₋₄alkoxyl which may be halogenated (for example, methoxymethoxy,methoxyethoxy, ethoxyethoxy, trifluoromethoxyethoxy,trifluoroethoxyethoxy or the like), formyl, a C₂₋₄ alkanoyl (forexample, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like) or the like, wherethe number of the substituents is preferably 1 to 3.

The substituent for the hydroxyl group which may be substituted as asubstituent of R^(e1) is exemplified by a substituent such as (1) analkyl which may be substituted (for example, a C₁₋₁₀ alkyl such asmethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, etc.);

(2) a cycloalkyl which may be substituted and may contain heteroatoms(for example, a C₃₋₇ cycloalkyl such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl or the like; a saturated, 5- to6-membered heterocyclic ring group containing 1 to 2 heteroatoms such astetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl,piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl,tetrahydrothiopyranyl or the like (preferably, tetrahydropyranyl or thelike); or the like is exemplified);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified);

(6) formyl or an acyl which may be substituted (for example, an alkanoylwhich has the carbon number of 2 to 4 (for example, acetyl, propionyl,butyryl, isobutyryl or the like), an alkylsulfonyl which has the carbonnumber of 1 to 4 (for example, methanesulfonyl, ethanesulfonyl or thelike) or the like is exemplified); and

(7) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified),

where examples of the substituents which may be possessed by (1) analkyl which may be substituted, (2) a cycloalkyl which may besubstituted, (3) an alkenyl which may be substituted, (4) a cycloalkenylwhich may be substituted, (5) an aralkyl which may be substituted, (6)an acyl which may be substituted and (7) an aryl which may besubstituted include a halogen (for example, fluorine, chlorine, bromine,iodine or the like), nitro, cyano, the hydroxyl group, the thiol groupwhich may be substituted (for example, thiol, a C₁₋₄ alkylthio or thelike), an amino group which may be substituted (for example, amino, amono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered cyclicring amino such as tetrahydropyrrole, piperazine, piperidine,morpholine, thiomorpholine, pyrrole, imidazole or the like, or thelike), the carboxyl group which may be esterified or amidated (forexample, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkylwhich may be halogenated (for example, trifluoromethyl, methyl, ethyl orthe like), a C₁₋₆ alkoxyl which may be halogenated (for example,methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, trifluoroethoxy orthe like; preferably, a C₁₋₄ alkoxyl which may be halogenated), formyl,a C₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), a C₁₋₄alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), a 5- to 6-membered, aromatic heterocyclic ring which may besubstituted [for example, an aromatic heterocyclic ring, which contains1 to 4 heteroatoms of 1 to 2 kinds selected from the nitrogen atom, thesulfur atom and the oxygen atom, such as furan, thiophene, pyrrole,imidazole, pyrazole, thiazole, oxazole, isothiazole, isoxazole,tetrazole, pyridine, pyrazine, pyrimidine, pyridazine, triazole or thelike; the substituent which may be possessed by said heteroaromatic ringis exemplified by a halogen (for example, fluorine, chlorine, bromine,iodine or the like), nitro, cyano, the hydroxyl group, the thiol group,an amino group, the carboxyl group, a C₁₋₄ alkyl which may behalogenated (for example, trifluoromethyl, methyl, ethyl or the like), aC₁₋₄ alkoxyl which may be halogenated (for example, methoxy, ethoxy,propoxy, butoxy, trifluoromethoxy, trifluoroethoxy or the like), formyl,a. C₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), a C₁₋₄alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), where the number of the substituents is preferably 1 to 3.], orthe like, where the number of the substituents is preferably 1 to 3.

The substituent for the thiol group which may be substituted as asubstituent of R^(e1) is exemplified by a substituent similar to “asubstituent for the hydroxyl group which may be substituted as asubstituent of R^(e1)” among which preferable is

(1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like is exemplified);

(3) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified); and

(4) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified),

where examples of the substituents which may be possessed by (1) analkyl which may be substituted, (2) a cycloalkyl which may besubstituted, (3) an aralkyl which may be substituted and (4) an arylwhich may be substituted, which are described above, include a halogen(for example, fluorine, chlorine, bromine, iodine or the like), nitro,cyano, the hydroxyl group, the thiol group which may be substituted (forexample, thiol, a C₁₋₄ alkylthio or the like), an amino group which maybe substituted (for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄alkylamino, a 5- to 6-membered cyclic ring amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), the carboxyl group whichmay be esterified or amidated (for example, carboxyl, a C₁₋₄alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄alkylcarbamoyl or the like), a C₁₋₄ alkoxyl which may be halogenated(for example, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy or the like), a. C₁₋₄ alkoxy-C₁₋₄ alcoxy which may behalogenated (for example, methoxymethoxy, methoxyethoxy, ethoxyethoxy,trifluoromethoxyethoxy, trifluoroethoxyethoxy or the like), formyl, aC₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), a C₁₋₄alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), where the number of the substituents is preferably 1 to 3.

A substituent for an amino group which may be substituted as asubstituent of R^(e1) is exemplified by an amino group which may have 1to 2 substituents similar to “a substituent for the hydroxyl group whichmay be substituted as a substituent of R^(e1)”, among which preferableis (1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkylsuch as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) formyl, or an acyl which may be substituted (for example, analkanoyl which has the carbon number of 2 to 4 (for example, acetyl,propionyl, butyryl, isobutyryl or the like), an alkylsulfonyl which hasthe carbon number of 1 to 4 (for example, methanesulfonyl,ethanesulfonyl or the like) or the like is exemplified); and

(6) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified),

where examples of the substituents which may be possessed by (1) analkyl which may be substituted, (2) a cycloalkyl which may besubstituted, (3) an alkenyl which may be substituted, (4) a cycloalkenylwhich may be substituted, (5) an acyl which may be substituted and (6)an aryl which may be substituted, which are described above, include ahalogen (for example, fluorine, chlorine, bromine, iodine or the like),nitro, cyano, the hydroxyl group, the thiol group which may besubstituted (for example, thiol, a C₁₋₄ alkylthio or the like), an aminogroup which may be substituted (for example, amino, a mono-C₁₋₄alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered cyclic ring aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole or the like, or the like), thecarboxyl group which may be esterified or amidated (for example,carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl,a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkoxy which may behalogenated (for example, methoxy, ethoxy, propoxy, butoxy,trifluoromethoxy, trifluoroethoxy or the like), C₁₋₄ alkoxy-C₁₋₄ alkoxywhich may be halogenated (for example, methoxymethoxy, methoxyethoxy,ethoxyethoxy, trifluoromethoxyethoxy, trifluoroethoxyethoxy or the like)formyl, a C₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), aC₁₋₄ alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), where the number of the substituents is preferably 1 to 3.

Also, as for the substituents for an amino group which may besubstituted as a substituent of R^(e1), the substituents for the aminogroup may bind together to form a cyclic ring amino group (for example,a cyclic ring amino group which is formed by removing one hydrogen fromthe nitrogen atom constituting the ring of a 5- to 6-membered cyclicring such as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole or the like, and has a bond on thenitrogen atom). Said cyclic ring amino group may have substituents, andsuch substituents are exemplified by a halogen (for example, fluorine,chlorine, bromine, iodine or the like), nitro, cyano, a hydroxyl group,a thiol group which may be substituted (for example, thiol, a C₁₋₄alkylthio or the like), an amino group which may be substituted (forexample, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to6-membered cyclic ring amino such as tetrahydropyrrole, piperazine,piperidine, morpholine, thiomorpholine, pyrrole, imidazole or the like,or the like), the carboxyl group which may be esterified or amidated(for example, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkoxywhich may be halogenated (for example, methoxy, ethoxy, propoxy, butoxy,trifluoromethoxy, trifluoroethoxy or the like), a C₁₋₄ alkoxy-C₁₋₄alkoxy which may be halogenated (for example, methoxymethoxy,methoxyethoxy, ethoxyethoxy, trifluoromethoxyethoxy,trifluoroethoxyethoxy or the like), formyl, a C₂₋₄ alkanoyl (forexample, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like), where the numberof the substituents is preferably 1 to 3.

The acyl which may be substituted as a substituent of R^(e1) isexemplified by a group, wherein the carbonyl group or the sulfonyl groupis bonded with

-   (1) hydrogen,-   (2) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl    such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,    sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl,    octyl, nonyl, decyl or the like, preferably a lower (C₁₋₆) alkyl, or    the like is exemplified);-   (3) a cycloalkyl which may be substituted (for example, a C₃₋₇    cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,    cycloheptyl or the like);-   (4) an alkenyl which may be substituted (for example, an alkenyl    which has the carbon number of 2 to 10 such as allyl, crotyl,    2-pentenyl, 3-hexenyl or the like, preferably a lower (C₂₋₆)    alkenyl, or the like is exemplified);-   (5) a cycloalkenyl which may be substituted (for example, an    cycloalkenyl which has the carbon number of 3 to 7 such as    2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,    2-cyclohexenylmethyl or the like, or the like is exemplified); or-   (6) a 5- to 6-membered, monocyclic ring aromatic group which may be    substituted (for example, phenyl, pyridyl or the like is    exemplified), which is bonded with a carbonyl group or a sulfonyl    group, (for example, acetyl, propionyl, butyryl, isobutyryl,    valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl, octanoyl,    cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl,    cycloheptanecarbonyl, crotonyl, 2-cyclohexenecarbonyl, benzoyl,    nicotinoyl, methanesulfonyl, ethanesulfonyl or the like), where    examples of the substituents which may be possessed by (2) the alkyl    which may be substituted, (3) the cycloalkyl which may be    substituted, (4) the alkenyl which may be substituted, (5) the    cycloalkenyl which may be substituted and (6) the 5- to 6-membered,    monocyclic ring aromatic group which may be substituted, which are    described above, include a halogen (for example, fluorine, chlorine,    bromine, iodine or the like), nitro, cyano, a hydroxyl group, a    thiol group which may be substituted (for example, thiol, a C₁₋₄    alkylthio or the like), an amino group which may be substituted (for    example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5-    to 6-membered cyclic ring amino such as tetrahydropyrrole,    piperazine, piperidine, morpholine, thiomorpholine, pyrrole,    imidazole or the like, or the like), a carboxyl group which may be    esterified or amidated (for example, carboxyl, a C₁₋₄    alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄    alkylcarbamoyl or the like), a C₁₋₄ alkoxy which may be halogenated    (for example, methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,    trifluoroethoxy or the like), a C₁₋₄ alkoxy-C₁₋₄ alkoxy which may be    halogenated (for example, methoxymethoxy, methoxyethoxy,    ethoxyethoxy, trifluoromethoxyethoxy, trifluoroethoxyethoxy or the    like), formyl, a C₂₋₄ alkanoyl (for example, acetyl, propionyl or    the like), a C₁₋₄ alkylsulfonyl (for example, methanesulfonyl,    ethanesulfonyl or the like), where the number of the substituents is    preferably 1 to 3.

The carboxyl group which may be esterified as a substituent of R^(e1) isexemplified by a group, wherein the carbonyloxy group is bonded with

-   (1) hydrogen,-   (2) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl    such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,    sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl,    octyl, nonyl, decyl or the like, preferably a lower (C₁₋₆) alkyl, or    the like is exemplified);-   (3) a cycloalkyl which may be substituted and may contain    heteroatoms (for example, a C₃₋₇ cycloalkyl such as cyclopropyl,    cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or the like);-   (4) an alkenyl which may be substituted (for example, an alkenyl    which has the carbon number of 2 to 10 such as allyl, crotyl,    2-pentenyl, 3-hexenyl or the like, preferably a lower (C₂₋₆)    alkenyl, or the like is exemplified);-   (5) a cycloalkenyl which may be substituted (for example, an    cycloalkenyl which has the carbon number of 3 to 7 such as    2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,    2-cyclohexenylmethyl or the like, or the like is exemplified); or-   (6) an aryl which may be substituted (for example, phenyl, naphthyl    or the like is exemplified), preferably carboxyl, a lower (C₁₋₆)    alkoxycarbonyl and an aryloxycarbonyl (for example, methoxycarbonyl,    ethoxycarbonyl, propoxycarbonyl, phenoxycarbonyl, naphthoxycarbonyl    or the like), where examples of the substituents which may be    possessed by (2) an alkyl which may be substituted, (3) a cycloalkyl    which may be substituted, (4) an alkenyl which may be    substituted, (5) a cycloalkenyl which may be substituted and (6) an    aryl which may be substituted, which are described above, include a    halogen (for example, fluorine, chlorine, bromine, iodine or the    like), nitro, cyano, a hydroxyl group, a thiol group which may be    substituted (for example, thiol, a C₁₋₄ alkylthio or the like), an    amino group which may be substituted (for example, amino, a    mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered    cyclic ring amino such as tetrahydropyrrole, piperazine, piperidine,    morpholine, thiomorpholine, pyrrole, imidazole or the like, or the    like), the carboxyl group which may be esterified or amidated (for    example, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄    alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkoxy    which may be halogenated (for example, methoxy, ethoxy, propoxy,    butoxy, trifluoromethoxy, trifluoroethoxy or the like), a C₁₋₄    alkoxy-C₁₋₄ alkoxy which may be halogenated (for example,    methoxymethoxy, methoxyethoxy, ethoxyethoxy, trifluoromethoxyethoxy,    trifluoroethoxyethoxy or the like), formyl, a C₂₋₄ alkanoyl (for    example, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (for    example, methanesulfonyl, ethanesulfonyl or the like), where the    number of the substituents is preferably 1 to 3.

The aromatic group for an aromatic group which may be substituted as asubstituent of R^(e1) is exemplified by a 5-to 6-membered, same elementor heterocyclic ring aromatic group such as phenyl, pyridyl, furyl,thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl,isothiazolyl, isooxazolyl, tetrazolyl, pirazinyl, pyrimidinyl,pyridazinyl, triazolyl or the like, a condensed heterocyclic ringaromatic group such as benzofuran, indole, benzothiophene, benzoxazole,benzthiazole, indazole, benzimidazole, quinoline, isoquinoline,quinoxaline, phthalazine, quinazoline, cinnoline or the like, or thelike. Examples of the substituents for these aromatic groups include ahalogen (for example, fluorine, chlorine, bromine, iodine or the like),nitro, cyano, the hydroxyl group, the thiol group which may besubstituted (for example, thiol, a C₁₋₄ alkylthio or the like), an aminogroup which may be substituted (for example, amino, a mono-C₁₋₄alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered cyclic ring aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole or the like, or the like), thecarboxyl group which may be esterified or amidated (for example,carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl,a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkyl which may behalogenated (for example, trifluoromethyl, methyl, ethyl or the like), aC₁₋₄ alkoxy which may be halogenated (for example, methoxy, ethoxy,propoxy, butoxy, trifluoromethoxy, trifluoroethoxy or the like), formyl,a C₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), a C₁₋₄alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), where the number of the substituents is preferably 1 to 3.

One to four (preferably one or two) of these substituents of R^(e1) maybe the same or different and present at any position. Also, in the casewhere “a 5- to 6-membered cyclic ring” of “a 5- to 6-membered cyclicring which may be substituted”, which is represented by R^(e1), has 2 ormore substituents, 2 substituents of them may be bonded together toform, for example, a lower (C₁₋₆) alkylene (for example, trimethylene,tetramethylene or the like), a lower (C₁₋₆) alkyleneoxy (for example,—CH₂—O—CH₂—, —O—CH₂—CH₂—, —O—CH₂—CH₂—CH₂—, —O—CH₂—CH₂—CH₂—CH₂—,—O—C(CH₃)(CH₃)—CH₂—CH₂— or the like), a lower (C₁₋₆) alkylenethio (forexample, —CH₂—S—CH₂—, —S—CH₂—CH₂—, —S—CH₂—CH₂—CH₂—, —S—CH₂—CH₂—CH₂—CH₂—,—S—C(CH₃)(CH₃)—CH₂—CH₂— or the like), a lower (C₁₋₆) alkylenedioxy (forexample, —O—CH₂—O—, —O—CH₂—CH₂—O—, —O—CH₂—CH₂—CH₂—O— or the like), alower (C₁₋₆) alkylenedithio (for example, —S—CH₂—S—, —S—CH₂—CH₂—S—,—S—CH₂—CH₂—CH₂—S— or the like), an oxy-lower (C₁₋₆) alkylenamino (forexample, —O—CH₂—NH—, —O—CH₂—CH₂—NH— or the like), an oxy-lower (C₁₋₆)alkylenethio (for example, —O—CH₂—S—, —O—CH₂—CH₂—S— or the like), alower (C₁₋₆) alkylenamino (for example, —NH—CH₂—CH₂—, —NH—CH₂—CH₂—CH₂—or the like), a lower (C₁₋₆) alkylenediamino (for example, —NH—CH₂—NH—,—NH—CH₂—CH₂—NH— or the like), a thia-lower (C₁₋₆) alkylenamino (forexample, —S—CH₂—NH—, —S—CH₂—CH₂—NH— or the like), a lower (C₂₋₆)alkenylene (for example, —CH₂—CH═CH—, —CH₂—CH₂—CH═CH—,—CH₂—CH═CH—CH₂—CH₂— or the like), a lower (C₄₋₆) alkadienylene (forexample, —CH═CH—CH═CH— or the like) or the like.

Furthermore, the bivalent group which is formed by binding each other 2substituents of R^(e1) may have 1 to 3 substituents similar to “thesubstituent” which may be possessed by “a 5- to 6-membered cyclic ring”of “a 5- to 6-membered cyclic ring which may be substituted”, which isrepresented by R^(e1), (a halogen atom, nitro, cyano, an alkyl which maybe substituted, a cycloalkyl which may be substituted, the hydroxylgroup which may be substituted, the thiol group which may be substituted(the sulfur atom may be oxidized to form a sulfinyl group which may besubstituted or a sulfonyl group which may be substituted), an aminogroup which may be substituted, an acyl which may be substituted, thecarboxyl group which may be esterified or amidated, an aromatic groupwhich may be substituted and the like).

“The substituent” which may be possessed by “a 5- to 6-membered cyclicring” of “a 5- to 6-membered cyclic ring which may be substituted”,which is represented by R^(e1), is exemplified particularly by a lower(C₁₋₄) alkyl which may be halogenated or alkoxylated with a lower (C₁₋₄)alkyl (for example, methyl, ethyl, t-butyl, trifluoromethyl,methoxymethyl, ethoxymethyl, propoxymethyl, butoxymethyl, methoxyethyl,ethoxyethyl, propoxyethyl, butoxyethyl, or the like), a lower (C₁₋₄)alkoxyl which may be halogenated or alkoxylated with a lower (C₁₋₄)alkyl (for example, methoxy, ethoxy, propoxy, butoxy, t-butoxy,trifluoromethoxy, methoxymethoxy, ethoxymethoxy, propoxymethoxy,butoxymethoxy, methoxyethoxy, ethoxymethoxy, propoxyethoxy,butoxyethoxy, methoxypropoxy, ethoxypropoxy, propoxypropoxy,butoxypropoxy or the like), a halogen (for example, fluorine, chlorineor the like), nitro, cyano, an amino group which may be substituted with1 to 2 of a lower (C₁₋₄) alkyl, formyl or a lower (C₂₋₄) alkanoyl (forexample, amino, methylamino, dimethylamino, formylamino, acetylamino orthe like), a 5- to 6-membered cyclic ring amino group (for example,1-pyrrolidinyl, 1-piperazinyl, 1-piperidinyl, 4-morpholino,4-thiomorpholino, 1-imidazolyl, 4-tetrahydropyranyl or the like) or thelike.

“A bivalent group, in which the number of atoms constituting thestraight-chain portion is 1 to 4”, represented by X^(e1) and X^(e2), isexemplified by, for example, —(CH₂)_(ea′)— [ea′ represents an integer of1 to 4 (preferably, an integer of 1 to 2)], —(CH₂)_(eb′)—X^(e3)— [eb′represents an integer of 0 to 3 (preferably, an integer of 0 to 1) andX^(e3) represents an imino group which may be substituted (for example,an imino group which may be substituted with a lower (C₁₋₆) lower alkyl,a lower (C₃₋₇) cycloalkyl, formyl, a lower (C₂₋₇) lower alkanoyl, alower (C₁₋₆) lower alkoxycarbonyl or the like), the carbonyl group, theoxygen atom, the sulfur atom which may be oxidized by the oxygen atom(for example, —S(O)_(em)— (em represents an integer of 0 to 2) or thelike)], —CH═CH—, —C≡C—, —CO—NH—, —SO₂—NH— or the like. Although thesegroups may be bonded with W^(e) through either of the left or rightbond, it is preferable to be bonded with W^(e) through the right hand inthe case of X^(e1), whereas it is preferable to be bonded with W^(e)through the left hand in the case of X^(e2).

As for X^(e1), a bond, —(CH₂)_(eb′)—O— [eb′ is an integer of 0, 1 or 2(preferably, an integer of 0 to 1), —C≡C— or the like is preferable, anda bond is more preferable.

As for X^(e2), —(CH₂)_(ea″)— [ea″ is an integer of 1 to 2],—(CH₂)_(eb″)—X^(e3)— [eb″ is an integer of 0 to 1 and X^(e3) is an iminogroup which may be substituted, the carbonyl group, the oxygen atom, thesulfur atom which may be oxidized by the oxygen atom], —CH═CH—, —CO—NH—,—SO₂—NH— or the like is preferable, and —CO—NH— is more preferable.

In the above-mentioned formula (eI), a bivalent group which isrepresented by formula representd by W^(e)

(wherein each of ring A^(e) and ring B^(e) is a 5- to 7-membered cyclicring group which may be substituted, each of E^(e1) and E^(e4)represents the carbon atom which may be substituted or the nitrogen atomwhich may be substituted, each of Ee₂ and E^(e3) represents the carbonatom which may be substituted or the nitrogen atom which may besubstituted, the sulfur atom which may be oxidized (for example,—S(O)_(em)— (em represents an integer of 0 to 2) or the like) or theoxygen atom and each of ea and eb represents to be a single bond or adouble bond) represents which the bonding with adjacent X^(e1) andX^(e2) is made in a mode which is shown respectively by

(wherein each of the symbols has the meaning defined above).

In the above-mentioned formula (eI), “a 5- to 7-membered cyclic ring” of“a 5- to 7-membered cyclic ring which may be substituted”, which isrepresented by A^(e), is exemplified by a 5- to 7-membered (preferably,5- to 6-membered, saturated or unsaturated alicyclic hydrocarbon such asa C₅₋₇ cycloalkane (for example, cyclopentane, cyclohexane, cycloheptaneor the like), a C₅₋₇ cycloalkene (for example, 1-cyclopentene,2-cyclopentene, 3-cyclopentene, 2-cyclohexene, 3-cyclohexene or thelike), a C₅₋₆ cycloalkadiene (for example, 2,4-cyclopentadiene,2,4-cyclohexadiene, 2,5-cyclohexadiene or the like); a 6-memberedaromatic hydrocarbon such as benzene; a 5- to 7-membered, aromaticheterocyclic ring, a saturated or unsaturated non-aromatic heterocyclicring (aliphatic heterocyclic ring) or the like, which contains at leastone (preferably, 1 to 4, more preferably 1 to 2) of heteroatoms of 1 to3 kinds (preferably, 1 to 2 kinds) selected from the oxygen atom, thesulfur atom and the nitrogen atom; or the like.

Herein, “an aromatic heterocyclic ring” is exemplified by a 5- to7-membered, aromatic monocyclic heterocyclic ring (for example, furan,thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole,imidazole, pyrazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole,1,3,4-oxadiazole, furazane, 1,2,3-thiadiazole, 1,2,4-thiadiazole,1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine,pyridazine, pyrimidine, pyrazine, triazine or the like) or the like, and“a non-aromatic heterocyclic ring” is exemplified by, for example, a 5-to 7-membered (preferably, 5- to 6-membered), saturated or unsaturatednon-aromatic heterocyclic ring (aliphatic heterocyclic ring) such aspyrrolidine, tetrahydrofuran, thiolan, piperidine, tetrahydropyran,morpholine, thiomorpholine, piperazine, pyran, oxepine, thiepin, azepineor the like, or a 5- to 6-membered, non-aromatic heterocyclic ring,where a part or all of the double bonds in the above-mentioned aromaticmonocyclic heterocyclic ring are saturated, or the like.

As for “a 5- to 7-membered cyclic ring” of “a 5- to 7-membered cyclicring which may be substituted”, which is represented by A^(e), a 5- to6-membered, aromatic ring is preferable, and further benzene, furan,thiophene, pyrrole, pyridine (preferably, 6-membered) or the like ispreferable, where benzene is particularly preferable.

“The substituent” which may be possessed by “a 5- to 7-membered cyclicring” of “a 5- to 7-membered cyclic ring which may be substituted”,which is represented by A^(e), is exemplified by a group similar to “thesubstituent” which may be possessed by “a 5- to 6-membered cyclic ring”of “a 5- to 6-membered cyclic ring which may be substituted”, which isrepresented by R^(e1). Also, 1 to 4 (preferably, 1 to 2) of thesubstituent for A^(e) may be present at any positions of the same ordifferent rings, and the substituent may be possessed at anysubstitutable position, whether it is any of the positions which arerepresentd by E^(e1) and E^(e2) or any of other positions.

In the above-mentioned formula (eI), “a 5- to 7-membered cyclic ring” of“a 5- to 7-membered cyclic ring which may be substituted”, which isrepresented by B, is exemplified by a 5- to 7-membered cyclic ring whichmay have substituents at optional, substitutable positions, which isrepresented by formula

or the like.

In the above-mentioned formula (eI), the bivalent group which isrepresented by Y^(e) is a bivalent group, with which ring B^(e) forms a5- to 7-membered cyclic ring which may be substituted, and isexemplified by a bivalent group such as, for example,

-   (1) —(CH₂)_(ea1)—O—(CH₂)_(ea2)— (each of ea1 and ea2 represents 0, 1    or 2 in the same or different manner. Hereupon, the sum of ea1 and    ea2 is 2 or less), —O—(CH═CH)—, —(CH═CH)—O—,-   (2) —(CH₂)_(eb1)—S(O)_(em)—(CH₂)_(eb2)— (em represents an integer of    0 to 2, and each of eb1 and eb2 represents 0, 1 or 2 in the same or    different manner. Hereupon, the sum of b1 and b2 is 2 or less),    —S(O)_(em)—(CH═CH)—, —(CH═CH)—S(O)_(em)—,-   (3) —(CH₂)_(ed1)— (de1 represents 1, 2 or 3), —CH₂—(CH═CH)—,    (CH═CH)—CH₂—, —CH═CH—, —CH═,-   (4) —(CH₂)_(e1)—NH—(CH₂)_(e2)— (each of e1 and e2 represents 0, 1 or    2 in the same or different manner. Hereupon, the sum of e1 and e2 is    2 or less), —NH—(CH═CH)—, —(CH═CH)—NH—,    —(CH₂)_(e6)—(N═CH)—(CH₂)_(e7)—, —(CH₂)_(e7)—(CH═N)—(CH₂)_(e6)—    (eIther of e6 and e7 represents 0, and the other represents 0 or 1),    —(CH₂)_(e8)—(N═N)—(CH₂)_(e9)— (eIther of e8 and e9 represents 0, and    the other represents 0 or 1) or the like. Specifically, the bivalent    group is exemplified by, for example, a bivalent group such as —O—,    —O—CH₂—, —O—CH₂—CH₂—, —O—CH═CH—, —S(O)_(em)— (em represents an    integer of 0 to 2), —S(O)_(em)—CH₂— (em represents an integer of 0    to 2), —S(O)_(em)—CH₂—CH₂— (em represents an integer of 0 to 2),    —S(O)_(em)—(CH═CH)—, (em represents an integer of 0 to 2), —CH₂—,    —(CH₂)₂—, —(CH₂)₃—, —CH═, —CH═CH—, —CH═CH—CH₂—, —CH₂—CH═CH—, —NH—,    —N═CH—, —CH═N—, —N═N— (respectively, the bonding represented starts    from ring A) or the like.

In addition, said bivalent group may have a substituent, and saidsubstituent is exemplified by a group similar to “the substituent” whichmay be possessed by “a 5- to 6-membered cyclic ring” of “a 5- to6-membered cyclic ring which may be substituted”, which is representedby R^(e1), oxo and the like, where a lower (C₁₋₃) alkyl (for example,methyl, ethyl, propyl or the like), phenyl, oxo, a hydroxyl group or thelike is particularly preferable. Furthermore, said bivalent group may be—O—C(O)— (the bonding represented starts from ring A) or the like. Thesubstituent for such a bivalent group may be present at any same ordifferent positions of 1 to 4 (preferably, 1 to 2). The substituentposition may be any position which is substitutable to said bivalentgroup.

As the bivalent group which is represented by Y^(e), a group such as—Y^(e′)—(CH₂)_(em′)— (Y^(e′) is —S(O)_(em) (em is an integer of 0 to 2),—O—, —NH— or —CH₂—, and em′ is an integer of 0 to 2), —CH═, —CH═CH—,—N═CH—, —(CH₂)_(em′)—Y^(e′)— (Y^(e′) is —S(O)_(em)— (em is an integer of0 to 2), —O—, —NH— or —CH₂—, and em′ is an integer of 0 to 2), —CH═N— orthe like, with starting the bonding representd from ring A^(e), ispreferable, where a group such as —Y^(e′)—(CH₂)_(em′)— (Y^(e′) is—S(O)_(em)— (em is an integer of 0 to 2), —O—, —NH— or —CH₂—, and em′ isan integer of 0 to 2), —CH═, —CH═CH—, —N═CH— or the like, with startingthe bonding representd from ring A^(e), is more preferable, and a group(ring B^(e) is a 5- to 7-membered ring which may be substituted) such as—Y^(e′)—(CH₂)₂—(Y^(e′) represents —S(O)_(em)— (em represents an integerof 0 to 2), —O—, —NH— or —CH₂—), with starting the bonding representdfrom ring A^(e), is most preferable.

“The substituent” which may be possessed by “a 5- to 7-membered cyclicring” of “a 5- to 7-membered cyclic ring which may be substituted”,which is represented by B^(e), is exemplified by a group similar to “thesubstituent” which may be possessed by “a 5- to 6-membered cyclic ring”of “a 5- to 6-membered cyclic ring which may be substituted”, which isrepresented by R^(e1). Also, such a substituent for B^(e) may be presentat any positions of 1 to 4 (preferably, 1 to 2) of the same or differentrings, but it is preferable that the position of E_(e3) isunsubstituted.

In the above-mentioned formula (eI), it is preferable that each ofE_(e3) and E_(e4) is the carbon atom which may be substituted(preferably, the carbon atom which is not substituted), and eb is adouble bond.

In the above-mentioned formula (eI), “a bivalent cyclic ring group”representd by Z^(e1) is exemplified by a group which is formed byremoving two hydrogen atoms from a group similar to “a 5- to 6-memberedcyclic ring” of “a 5- to 6-membered cyclic ring which may besubstituted”, or the like, where a bivalent cyclic ring group, which isformed by removing two hydrogen atoms from benzene, furan, thiophene,pyridine, cyclopentane, cyclohexane, pyrrolidine, piperidine,piperazine, morpholine, thiomorpholine, tetrahydropyran or the like, ismore preferable, and a bivalent cyclic ring group, which is formed byremoving two hydrogen atoms from benzene, cyclohexane or piperidine(preferably, benzene) is most preferably used.

“A bivalent cyclic ring group” representd by Zel may have a substituentsimilar to “a substituent” which is possessed by “a 5- to 6-memberedcyclic ring” of “a 5- to 6-membered cyclic ring which may besubstituted”, but it is preferable not to have a substituent other thanX^(e2) and Z^(e2), and also it is preferable that the substitutionposition for Z^(e2) is para to X^(e2) in the case where Z^(e1) is a6-membered, bivalent cyclic ring group (preferably, phenylene).

In the above-mentioned formula (eI), “a bivalent group, in which thenumber of hydrogen atoms constituting the straight-chain portion is 1 to4”, which is represented by Z^(e2), is exemplified by a bivalent groupwhich has a hydrocarbon chain having the carbon number of 1 to 4, whichmay be substituted (for example, a C₁₋₄ alkylene, a C₂₋₄ alkenylene orthe like, preferably a C₁₋₃ alkylene, more preferably methylene), or thelike.

A bivalent group, which is represented by Z^(e2), may be any grouphaving a bivalent chain, in which the number of atoms constituting thestraight-chain portion is 1 to 4, and is exemplified by, for example, analkylene chain represented by —(CH₂)_(ek1)— (ek1 is an integer of 1 to4), an alkenylene chain represented by —(CH₂)_(ek2)—(CH═CH)—(CH₂)_(ek3)—(each of ek2 and ek3 represents an integer of 0, 1 or 2 in the same ordifferent manner. Hereupon, the sum of ek2 and ek3 is 2 or less) or thelike.

A bivalent group, which is represented by X^(e1), X^(e2) and Z^(e2), mayhave a substituent at an optional position (preferably, on the carbonatom), where such a substituent may be any one that is capable of beingbonded to a bivalent chain constituting the straight-chain portion, isexemplified by, for example, a lower (C₁₋₆) alkyl (for example, methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl or the like), a lower (C₃₋₇)cycloalkyl (for example, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl or the like), formyl, a lower (C₂₋₇) alkanoyl(for example, acetyl, propionyl, butyryl or the like), a phosphono groupwhich may be esterified, the carboxyl group which may be esterified, thehydroxyl group, oxo or the like, where preferably a lower alkyl havingthe carbon number of 1 to 6 (preferably a C₁₋₃ alkyl), the hydroxylgroup, oxo or the like is exemplified.

Said phosphono group which may be esterified is exemplified by a grouprepresented by —P(O)(OR^(e7))(OR^(e8)) [wherein each of R^(e7) andR^(e8) is hydrogen, an alkyl group having the carbon number of 1 to 6 ora cycloalkyl group having the carbon number of 3 to 7, and may be bondedtogether to form a 5- to 7-membered cyclic ring].

In the above-mentioned formula, an alkyl group having the carbon numberof 1 to 6, which is represented by R^(e7) and R^(e8), is exemplified bymethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl or the like, and acycloalkyl having the carbon number of 3 to 7 is exemplified bycyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or thelike), where a lower alkyl having the carbon number of 1 to 6 isexemplified preferably, and a lower alkyl having the carbon number of 1to 3 is exemplified more preferably. R^(e7) and R^(e8) may be the sameor different, but it is preferable to be the same. Also, in the casewhere R^(e7) and R^(e8) are bonded together to form a 5- to 7-memberedcyclic ring, R^(e7) and R^(e8) are bonded together to form astraight-chained C₂₋₄ alkylene side chain represented by —(CH₂)₂—,—(CH₂)₃—, —(CH₂)₄—. Said side chain may have substituents, and such asubstituent is exemplified by, for example, the hydroxyl group, ahalogen or the like.

The carboxyl group, which is esterified for the carboxyl group which maybe esterified, is exemplified by a group, wherein the carboxyl group isbonded with an alkyl group having the carbon number of 1 to 6 or acycloalkyl group having the carbon number of 3 to 7, such asmethoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl,tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl or the like.

A bivalent group, which is represented by Z^(e2), is exemplified by aC₁₋₃ alkylene which may be substituted, where a C₁₋₃ alkylene which maybe substituted with a C₁₋₃ alkyl, the hydroxyl group or oxo is morepreferable.

Furthermore, as for a bivalent group, which is represented by Z^(e2), agroup represented by -Z^(e′)-(CH₂)en- or —(CH₂)en-Z^(e′- (Z) ^(e′) is—CH(OH)—, —C(O)— or —CH₂—, en is an integer of 0 to 2 and each methylenegroup may have 1 to 2 groups of the same or different substituent), withstarting from the benzene ring, is preferable, a group represented by-Z^(e′)—(CH₂)en- (Z^(e′) represents —CH(OH)—, —C(O)— or —CH₂—, enrepresents an integer of 0 to 2 (preferably, en is 0) and each methylenegroup may have 1 to 2 groups of the same or different substituents),with starting from the benzene ring, is more preferable and methylene ismost preferable.

In the above-mentioned formula (eI), “an amino group” of “an amino groupwhich may be substituted, where the nitrogen atom may be converted intoa quaternary ammonium or the N-oxide” represented by R^(e2) isexemplified by an amino group which may have 1 to 2 substituents, anamino group which has 3 substituents, where the nitrogen atom may beconverted into a quaternary ammonium, or the like. In the case where thesubstituents on the nitrogen atom are 2 or more, these substituents maybe the same or different, and in the case where the substituents on thenitrogen atom are 3, the amino group may be of any type of —N⁺(R^(e))₃,—N⁺(R^(e))₂R^(e)′, —N⁺R^(e)R^(e)′R^(e)″ (each of R^(e), R^(e)′ andR^(e)″ is hydrogen or a substituent in a different manner). In addition,a counter anion for the amino group, in which the nitrogen atom isconverted into a quaternary ammonium, is exemplified by, in addition toan anion of a halogen atom (for example, Cl⁻, Br⁻, I⁻ or the like) orthe like, an anion derived from an inorganic acid such as hydrochloricacid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid andthe like, an anion derived from an organic acid such as formic acid,acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaricacid, maleic acid, citric acid, succinic acid, malic acid,methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid andthe like and an anion derived from an acidic amino acid such as asparticacid, glutamic acid and the like, where Cl⁻, Br⁻, I⁻ or the like is morepreferable.

Examples of substituents for said amino group include substituents suchas,

(1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₈cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cianooctyl or the like is exemplified);

(2-1) said cycloalkyl contains one heteroatom selected from the sulfuratom, the oxygen atom and the nitrogen atom, and may form oxirane,thiolan, aziridine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine,tetrahydropyran, tetrahydrothiopyran, tetrahydrothiopyran 1-oxide,piperidine or the like (preferably, a 6-membred ring such astetrahydropyran, tetrahydrothiopyran, piperidine or the like), where thebinding position with the amino group is preferably position 3 orposition 4 (preferably, position 4);

(2-2) also, said cycloalkyl may condensed with the benzene ring to forman indane (for example, indan-1-yl, indan-2-yl or the like),tetrahydronaphthalene, (for example, tetrahydronaphthalen-5-yl,tetrahydronaphthalen-6-yl or the like) or the like (preferably, indane,etc.);

(2-3) furthermore, said cycloalkyl may be crosslinked via astraight-chained, atom chain having the carbon number of 1 to 2 to forma crosslinked, cyclic hydrocarbon residue such as bicyclo[2.2.1]heptyl,bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl or thelike (preferably, a cycloalkyl having a crosslink via astraight-chained, atom chain having the carbon number of 1 to 2, or thelike, more preferably bicyclo[2.2.1]heptyl or the like);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified);

(6) formyl or an acyl which may be substituted (for example, an alkanoylwhich has the carbon number of 2 to 4 (for example, acetyl, propionyl,butyryl, isobutyryl or the like), an alkylsulfonyl which has the carbonnumber of 1 to 4 (for example, methanesulfonyl, ethanesulfonyl or thelike), an alkoxycarbonyl which has the carbon number of 1 to 4(methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or the like), anaralkyloxycarbonyl which has the carbon number of 7 to 10 (for example,benzyloxycarbonyl or the like) or the like is exemplified);

(7) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified); and

(8) a heterocyclic ring group which may be substituted (a group which isformed by removing one hydrogen atom from a 5- to 6-membered, aromaticheterocyclic ring, which contains 1 to 4 heteroatoms of 1 to 2 kindsselected from the nitrogen atom, the sulfur atom and the oxygen atom,such as furan, thiophene, pyrrole, imidazole, pyrazole, thiazole,oxazole, isothiazole, isoxazole, tetrazole, pyridine, pyrazine,pyrimidine, pyridazine, triazole or the like, a group which is formed byremoving one hydrogen atom from a 5- to 6-membered, non-aromaticheterocyclic ring, which contains 1 to 4 heteroatoms of 1 to 2 kindsselected from the nitrogen atom, the sulfur atom and the oxygen atom,such as tetrahydrofuran, tetrahydrothiophene, dithiolan, oxathiolan,pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine,pyrazoline, piperidine, piperazine, oxazine, oxadiazine, thiazine,thiadiazine, morpholine, thiomorpholine, pyran, tetrahydropyran or thelike, or the like; preferably, a group, which is formed by removing onehydrogen atom from a 5- to 6-membered, non-aromatic heterocyclic ring,or the like; and more preferably, a group, which is formed by removingone hydrogen atom from a 5- to 6-membered, non-aromatic heterocyclicring, which has one heteroatom, such as tetrahydrofuran, piperidine,tetrahydropyran, tetrahydrothiopyran or the like) and the like. Inaddition, the substituents of said amino group may be bonded each otherto form a 5- to 7-membered, cyclic amino such as piperidine, piperazine,morpholine, thiomorpholine or the like.

Examples of the substituents which may be possessed by (1) an alkylwhich may be substituted, (2) a cycloalkyl which may be substituted, (3)an alkenyl which may be substituted, (4) a cycloalkenyl which may besubstituted, (5) an aralkyl which may be substituted, (6) an acyl whichmay be substituted, (7) an aryl which may be substituted and (8) aheterocyclic ring group which may be substituted, which are describedabove, include a halogen (for example, fluorine, chlorine, bromine,iodine or the like), a lower (C₁₋₄) alkyl which may be halogenated, aC₁₋₄ alkoxyl which may be halogenated (for example, methoxy, ethoxy,propoxy, butoxy, trifluoromethoxy, trifluoroethoxy or the like), a C₁₋₄alkylenedioxy (for example, —O—CH₂—O—, —O—CH₂—CH₂—O— or the like),formyl, a C₂₋₄ alkanoyl (for example, acetyl, propionyl or the like), aC₁₋₄ alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or thelike), a phenyl-lower (C₁₋₄) alkyl, a C₃₋₇ cycloalkyl, cyano, nitro, ahydroxyl group, a thiol group which may be substituted (for example,thiol, a C₁₋₄ alkylthio or the like), an amino group which may besubstituted (for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄alkylamino, a 5- to 6-membered cyclic ring amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), the carboxyl group whichmay be esterified or amidated (for example, carboxyl, a C₁₋₄alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄alkylcarbamoyl or the like), a lower (C₁₋₄) alkoxycarbonyl, a lower(C₇₋₁₀) aralkyloxycarbonyl, the oxo group (preferably, a halogen, alower (C₁₋₄) alkyl which may be halogenated, a C₁₋₄ alkoxyl which may behalogenated, a phenyl-lower (C₁₋₄) alkyl, a C₃₋₇ cycloalkyl, cyano, ahydroxyl group or the like) and the like, where the number of thesubstituents is preferably 1 to 3.

In the above-mentioned formula (eI), “an amino group which may besubstituted, where the nitrogen atom may be converted into a quaternaryammonium or the N-oxide” representd by R^(e2), is preferably an aminogroup which may have 1 to 3 substituents selected from,

(1) a straight-chained or branched, lower (C₁₋₆) alkyl which may have 1to 3 groups of a halogen, cyano, a hydroxyl group or a C₃₋₇ cycloalkyl;

(2) a C₅₋₈ cycloalkyl which may have 1 to 3 groups of a halogen, a lower(C₁₋₄) alkyl which may be halogenated or a phenyl-lower (C₁₋₄) alkyl,may contain one heteroatom selected from the sulfur atom, the oxygenatom and the nitrogen atom, may be condensed with the benzene ring andmay be crosslinked via a straight-chained, atom chain having the carbonnumber of 1 to 2, (for example, cyclopentyl, cyclohexyl, cycloheptylcyclooctyl, tetrahydropyranyl, tetrahydrothiapyranyl, piperidinyl,indanyl, tetrahydronaphthalenyl, bicyclo[2.2.1]heptyl or the like);

(3) a phenyl-lower (C₁₋₄) alkyl which may have 1 to 3 groups of ahalogen, a lower (C₁₋₄) alkyl which may be halogenated or a C₁₋₄ alkoxylwhich may be halogenated;

(4) a phenyl which may have 1 to 3 groups of a halogen, a lower (C₁₋₄)alkyl which may be halogenated or a C₁₋₄ alkoxyl which may behalogenated; and

(5) a 5- to 6-membered, aromatic heterocyclic ring which may have 1 to 3groups of a halogen, a lower (C₁₋₄) alkyl which may be halogenated, aC₁₋₄ alkoxy which may be halogenated, a lower (C₁₋₄) alkoxy-(C₁₋₄) loweralkoxy which may be halogenated, a phenyl-lower (C₁₋₄) alkyl, cyano orthe hydroxyl (for example, a group which is formed by removing onehydrogen atom from furan, thiophene, pyrrole, pyridine or the like).

In the above-mentioned formula (eI), “a nitrogen-containing,heterocyclic ring” of “a nitrogen-containing, heterocyclic group whichmay be substituted and may contain the sulfur atom or the oxygen atom asa ring-constituting atom, where the nitrogen atom may be converted intoa quaternary ammonium or the N-oxide” is exemplified by a 5-to6-membered, aromatic heterocyclic ring, which may contain, in additionto one nitrogen atom, 1 to 3 heteroatoms of 1 to 2 kinds selected fromthe nitrogen atom, the sulfur atom and the oxygen atom, such as pyrrole,imidazole, pyrazole, thiazole, oxazole, isothiazole, isoxazole,tetrazole, pyridine, pyrazine, pyrimidine, pyridazine, triazole or thelike, a 5- to −8-membered, non-aromatic heterocyclic ring, which maycontain, in addition to one nitrogen atom, 1 to 3 hetero atoms of 1 to 2kinds selected from the nitrogen atom, the sulfur atom and the oxygenatom, such as pyrrolidine, pyrroline, imidazolidine, imidazoline,pyrazolidine, pyrazoline, piperidine, piperazine, oxazine, oxadiazine,thiazine, thiadiazine, morpholine, thiomorpholine, azacycloheptane,azacyclooctane (azokane) or the like, or the like, where each of thesenitrogen-containing, heterocyclic rings may be crosslinked via astraight-chained, atom chain having the carbon number of 1 to 2 and mayform a crosslinked, nitrogen-containing, heterocyclic ring such asazabicyclo[2.2.1]heptane, azabicyclo[2.2.2]octane (quinuclidine) or thelike (preferably, piperidine, which may have a crosslink via astraight-chained, atom chain having the carbon number of 1 to 2, or thelike).

Among the specific examples of the above-mentioned nitrogen-containingheterocyclic ring, pyridine, imidazole, pyrrolidine, piperidine,piperazine, morpholine, thiomorpholine and azabicyclo[2.2.2]octane(preferably, 6-membered, cyclic rings) are preferable.

The nitrogen atom of said “nitrogen-containing heterocyclic ring” may beconverted into a quaternary ammonium, or may be oxidized. In the casewhere the nitrogen atom of said “nitrogen-containing heterocyclic ring”is converted into a quaternary ammonium, a counter anion for “thenitrogen-containing heterocyclic ring group, in which the nitrogen atomis converted into a quaternary ammonium”, is exemplified by, in additionto an anion of a halogen atom (for example, Cl⁻, Br⁻, I⁻ or the like) orthe like, an anion derived from an inorganic acid such as hydrochloricacid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid andthe like, an anion derived from an organic acid such as formic acid,acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaricacid, maleic acid, citric acid, succinic acid, malic acid,methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid andthe like and an anion derived from an acidic amino acid such as asparticacid, glutamic acid and the like, where Cl⁻, Br⁻, I⁻ or the like is morepreferable.

Said “nitrogen-containing heterocyclic ring” may be bonded with abivalent group, which is represented by Z^(e2), via either of the carbonatom or the nitrogen atom and may be bonded on the carbon atomconstituting the cyclic ring, as in the case of 2-pyridyl, 3-pyridyl,2-piperidyl or the like, whereas a bonding as in the case of

or the like is preferable.

Examples of substituents of said “nitrogen-containing heterocyclic ring”include a halogen (for example, fluorine, chlorine, bromine, iodine orthe like), a lower (C₁₋₄) alkyl which may be substituted, a lower (C₁₋₄)alkoxyl which may be substituted, a phenyl which may be substituted, amono- or diphenyl-lower (C₁₋₄) alkyl which may be substituted, a C₃₋₇cycloalkyl which may be substituted, cyano, nitro, a hydroxyl group, athiol group which may be substituted (for example, thiol, a C₁₋₄alkylthio or the like), an amino group which may be substituted (forexample, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to6-membered cyclic ring amino such as tetrahydropyrrole, piperazine,piperidine, morpholine, thiomorpholine, pyrrole, imidazole or the like,or the like), the carboxyl group which may be esterified or amidated(for example, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a lower (C₁₋₄)alkoxycarbonyl, formyl, a (C₂₋₄) alkanoyl, a lower (C₁₋₄) alkylsulfonyl,a heterocyclic ring group which may be substituted (e.g. a group whichis formed by removing one hydrogen atom from a 5- to 6-membered,aromatic heterocyclic ring, which contains 1 to 4 heteroatoms of 1 to 2kinds selected from the nitrogen atom, the sulfur atom and the oxygenatom, such as furan, thiophene, pyrrole, imidazole, pyrazole, thiazole,oxazole, isothiazole, isoxazole, tetrazole, pyridine, pyrazine,pyrimidine, pyridazine, triazole or the like, a group which is formed byremoving one hydrogen atom from a 5- to 6-membered, non-aromaticheterocyclic ring, which contains 1 to 4 heteroatoms of 1 to 2 kindsselected from the nitrogen atom, the sulfur atom and the oxygen atom,such as tetrahydrofuran, tetrahydrothiophene, dithiolan, oxathiolan,pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine,pyrazoline, piperidine, piperazine, oxazine, oxadiazine, thiazine,thiadiazine, morpholine, thiomorpholine, pyran, tetrahydropyran,tetrahydrothiopyran or the like, or the like, where the number of thesubstituents is preferably 1 to 3. Also, the nitrogen in said“nitrogen-containing heterocyclic ring” may be oxidized.

Examples of the substituents, which may be possessed by “a lower (C₁₋₄)alkyl which may be substituted”, “a lower (C₁₋₄) alkoxyl which may besubstituted”, “a phenyl which may be substituted”, “a mono- ordiphenyl-lower (C₁₋₄) alkyl which may be substituted”, “a C₃₋₇cycloalkyl which may be substituted” and “a heterocyclic ring groupwhich may be substituted”, as the substituents which may be possessed bysaid “nitrogen-containing heterocyclic ring”, include, for example, ahalogen (for example, fluorine, chlorine, bromine, iodine or the like),a lower (C₁₋₄) alkyl which may be halogenated, a lower (C₃₋₁₀)cycloalkyl, a lower (C₃₋₁₀) cycloalkenyl, a C₁₋₄ alkoxy which may behalogenated (for example, methoxy, ethoxy, trifluoromethoxy,trifluoroethoxy or the like), formyl, a C₂₋₄ alkanoyl (for example,acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (for example,methanesulfonyl, ethanesulfonyl or the like), a C₁₋₃ alkylenedioxy (forexample, methylenedioxy, ethylenedioxy or the like), cyano, nitro, thehydroxyl group, the thiol group which may be substituted (for example,thiol, a C₁₋₄ alkylthio or the like), an amino group which may besubstituted (for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄alkylamino, a 5- to 6-membered cyclic ring amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), the carboxyl group whichmay be esterified or amidated (for example, carboxyl, a C₁₋₄alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄alkylcarbamoyl or the like), a lower (C₁₋₄) alkoxycarbonyl and the like,where the number of the substituents is preferably 1 to 3.

In the above-mentioned formula (eI), the substituent, which may bepossessed by “a nitrogen-containing heterocyclic ring” of “anitrogen-containing heterocyclic ring group which may be substituted andmay contain the sulfur atom or the oxygen atom as a ring-constitutingatom, where the nitrogen atom may be converted into a quaternaryammonium or the N-oxide” is exemplified preferably by (1) a halogen, (2)cyano, (3) a hydroxyl group, (4) a carboxyl group, (5) a lower (C₁₋₄)alkoxycarbonyl, (6) a lower (C₁₋₄) alkyl which may be substituted with ahalogen, a hydroxyl group or a lower (C₁₋₄) alkoxy, (7) a lower (C₁₋₄)alkoxy which may be substituted with a halogen, the hydroxyl group or alower (C₁₋₄) alkoxy, (8) a phenyl which may be substituted with ahalogen, a lower (C₁₋₄) alkyl, a hydroxyl group, a lower (C₁₋₄) alkoxyor a C₁₋₃ alkylenedioxy, (9) a mono- or diphenyl-lower (C₁₋₄) alkylwhich may be substituted with a halogen, a lower (C₁₋₄) alkyl, thehydroxyl group, a lower (C₁₋₄) alkoxy or a C₁₋₃ alkylenedioxy, (10) agroup which is formed by removing one hydrogen atom from a 5- to6-membered aromatic heterocyclic ring, such as furan, thiophene,pyrrole, pyridine or the like, or the like.

In the above-mentioned formula (eI), “a group which is bonded via thesulfur atom”, which is represented by R^(e2), is exemplified by a grouprepresented by —S(O)em-R^(eS) (wherein em represents an integer of 0 to2 and R^(eS) is a substituent). In the above-mentioned formula, examplesof the substituent representd by R^(eS) include, for example,

(1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like is exemplified);

(3) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified); and

(4) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified), where examples of the substituents which maybe possessed by (1) an alkyl which may be substituted, (2) a cycloalkylwhich may be substituted, (3) an aralkyl which may be substituted and(4) an aryl which may be substituted, which are described above, includea halogen (for example, fluorine, chlorine, bromine, iodine or thelike), nitro, cyano, a hydroxyl group, a thiol group which may besubstituted (for example, thiol, a C₁₋₄ alkylthio or the like), an aminogroup which may be substituted (for example, amino, a mono-C₁₋₄alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-membered cyclic ring aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole or the like, or the like), thecarboxyl group which may be esterified or amidated (for example,carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl,a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkyl which may behalogenated (for example, trifluoromethyl, methyl, ethyl or the like), aC₁₋₄ alkoxy which may be halogenated (for example, methoxy, ethoxy,trifluoromethoxy, trifluoroethoxy or the like), formyl, a C₂₋₄ alkanoyl(for example, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like) or the like, wherethe number of the substituents is preferably 1 to 3.

In the above-mentioned formula (eI), “the hydrocarbon group” for thehydrocarbon group which may be substituted, which is represented byR^(e5′) and R^(e6′), in “a group represented by formula

(wherein ek represents 0 or 1, the phosphorus atom may form aphosphonium salt when ek is 0, and each of R^(e5′) and R^(e6′) is ahydrocarbon group which may be substituted, a hydroxyl group which maybe substituted or an amino group which may be substituted (preferably,the hydrocarbon group which may be substituted or an amino group whichmay be substituted; more preferably the hydrocarbon group which may besubstituted) and R^(e5′) and R^(e6′) may bind each other to form acyclic ring group together with the adjacent phosphorus atom)”, which isrepresented by R^(e2)′ is exemplified by,

(1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) an alkinyl which may be substituted (for example, an alkinyl whichhas the carbon number of 2 to 10 such as ethinyl, 1-propinyl,2-propinyl, 1-butinyl, 2-pentinyl, 3-hexinyl or the like, preferably alower (C₂₋₆) alkinyl, or the like is exemplified);

(6) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified); and

(7) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified), where examples of the substituents which maybe possessed by (1) an alkyl which may be substituted, (2) a cycloalkylwhich may be substituted, (3) an alkenyl which may be substituted, (4) acycloalkenyl which may be substituted, (5) an alkinyl which may besubstituted, (6) an aralkyl which may be substituted and (7) an arylwhich may be substituted, which are described above, include a halogen(for example, fluorine, chlorine, bromine, iodine or the like), nitro,cyano, a hydroxyl group, a thiol group which may be substituted (forexample, thiol, a C₁₋₄ alkylthio or the like), an amino group which maybe substituted (for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄alkylamino, a 5- to 6-membered cyclic ring amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), the carboxyl group whichmay be esterified or amidated (for example, carboxyl, a C₁₋₄alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄alkylcarbamoyl or the like), a C₁₋₄ alkyl which may be halogenated (forexample, trifluoromethyl, methyl, ethyl or the like), a C₁₋₄ alkoxywhich may be halogenated (for example, methoxy, ethoxy,trifluoromethoxy, trifluoroethoxy or the like), formyl, a C₂₋₄ alkanoyl(for example, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like) or the like, wherethe number of the substituents is preferably 1 to 3.

The hydroxyl group which may be substituted, which is represented byR^(e5′) and R^(e6′) is exemplified by a hydroxyl group which may besubstituted by, for example, (1) an alkyl which may be substituted (forexample, a C₁₋₁₀ alkyl such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl,heptyl, octyl, nonyl, decyl or the like, preferably a lower (C₁₋₆)alkyl, or the like is exemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) an aralkyl which may be substituted (for example, a phenyl-C₁₋₄alkyl (for example, benzyl, phenethyl or the like) or the like isexemplified);

(6) formyl or an acyl which may be substituted (for example, an alkanoylwhich has the carbon number of 2 to 4 (for example, acetyl, propionyl,butyryl, isobutyryl or the like), an alkylsulfonyl which has the carbonnumber of 1 to 4 (for example, methanesulfonyl, ethanesulfonyl or thelike) or the like is exemplified); and

(7) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified).

Examples of the substituents which may be possessed by (1) an alkylwhich may be substituted, (2) a cycloalkyl which may be substituted, (3)an alkenyl which may be substituted, (4) a cycloalkenyl which may besubstituted, (5) an aralkyl which may be substituted, (6) an acyl whichmay be substituted and (7) an aryl which may be substituted, which aredescribed above, include a halogen (for example, fluorine, chlorine,bromine, iodine or the like), nitro, cyano, the hydroxyl group, thethiol group which may be substituted (for example, thiol, a C₁₋₄alkylthio or the like), an amino group which may be substituted (forexample, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to6-membered cyclic ring amino such as tetrahydropyrrole, piperazine,piperidine, morpholine, thiomorpholine, pyrrole, imidazole or the like,or the like), the carboxyl group which may be esterified or amidated(for example, carboxyl, a C₁₋₄ alkoxycarbonyl, carbamoyl, a mono-C₁₋₄alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or the like), a C₁₋₄ alkylwhich may be halogenated (for example, trifluoromethyl, methyl, ethyl orthe like), a C₁₋₄ alkoxy which may be halogenated (for example, methoxy,ethoxy, trifluoromethoxy, trifluoroethoxy or the like), formyl, a C₂₋₄alkanoyl (for example, acetyl, propionyl or the like), a C₁₋₄alkylsulfonyl (for example, methanesulfonyl, ethanesulfonyl or the like)and the like, where the number of the substituents is preferably 1 to 3.

Also, in the above-mentioned formula, R^(e5′) and R^(e6′) may bind eachother to form a cyclic ring group together with the adjacent phosphorusatom (preferably, a 5- to 7-membered cyclic ring). Such a cyclic ringgroup may have substituents and examples of said substituents include ahalogen (for example, fluorine, chlorine, bromine, iodine or the like),nitro, cyano, a hydroxyl group, a thiol group which may be substituted(for example, thiol, a C₁₋₄ alkylthio or the like), an amino group whichmay be substituted (for example, amino, a mono-C₁₋₄ alkylamino, adi-C₁₋₄ alkylamino, a 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), the carboxyl group whichmay be esterified or amidated (for example, carboxyl, a C₁₋₄alkoxycarbonyl, carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄alkylcarbamoyl or the like), a C₁₋₄ alkyl which may be halogenated (forexample, trifluoromethyl, methyl, ethyl or the like), a C₁₋₄ alkoxywhich may be halogenated (for example, methoxy, ethoxy,trifluoromethoxy, trifluoroethoxy or the like), formyl, a C₂₋₄ alkanoyl(for example, acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (forexample, methanesulfonyl, ethanesulfonyl or the like) and the like,where the number of the substituents is preferably 1 to 3.

In the above-mentioned formula (eI), a counter anion in the case wherethe phosphorus atom forms a phosphonium salt is exemplified by, inaddition to an anion of a halogen atom (for example, Cl⁻, Br⁻, I⁻ or thelike) or the like, an anion derived from an inorganic acid such ashydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid,phosphoric acid and the like, an anion derived from an organic acid suchas formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalicacid, tartaric acid, maleic acid, citric acid, succinic acid, malicacid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acidand the like and an anion derived from an acidic amino acid such asaspartic acid, glutamic acid and the like, where Cl⁻, Br⁻, I⁻ or thelike is more preferable.

An amino group which may be substituted, which is represented by R^(e5′)and R^(e6′), is exemplified by an amino group which may have 1 to 2groups such as,

(1) an alkyl which may be substituted (for example, a C₁₋₁₀ alkyl suchas methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl,decyl or the like, preferably a lower (C₁₋₆) alkyl, or the like isexemplified);

(2) a cycloalkyl which may be substituted (for example, a C₃₋₇cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like);

(3) an alkenyl which may be substituted (for example, an alkenyl whichhas the carbon number of 2 to 10 such as allyl, crotyl, 2-pentenyl,3-hexenyl or the like, preferably a lower (C₂₋₆) alkenyl, or the like isexemplified);

(4) a cycloalkenyl which may be substituted (for example, ancycloalkenyl which has the carbon number of 3 to 7 such as2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl or the like, or the like is exemplified);

(5) formyl or an acyl which may be substituted (for example, an alkanoylwhich has the carbon number of 2 to 4 (for example, acetyl, propionyl,butyryl, isobutyryl or the like), an alkylsulfonyl which has the carbonnumber of 1 to 4 (for example, methanesulfonyl, ethanesulfonyl or thelike) or the like is exemplified); and

(6) an aryl which may be substituted (for example, phenyl, naphthyl orthe like is exemplified).

Examples of the substituents which may be possessed by (1) an alkylwhich may be substituted, (2) a cycloalkyl which may be substituted, (3)an alkenyl which may be substituted, (4) a cycloalkenyl which may besubstituted, (5) an acyl which may be substituted and (6) an aryl whichmay be substituted, which are described above, include a halogen (forexample, fluorine, chlorine, bromine, iodine or the like), nitro, cyano,a hydroxyl group, a thiol group which may be substituted (for example,thiol, a C₁₋₄ alkylthio or the like), an amino group which may besubstituted (for example, amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄alkylamino, a 5- to 6-membered cyclic ring amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole or the like, or the like), a carboxyl group which maybe esterified or amidated (for example, carboxyl, a C₁₋₄ alkoxycarbonyl,carbamoyl, a mono-C₁₋₄ alkylcarbamoyl, a di-C₁₋₄ alkylcarbamoyl or thelike), a C₁₋₄ alkyl which may be halogenated (for example,trifluoromethyl, methyl, ethyl or the like), a C₁₋₄ alkoxy which may behalogenated (for example, methoxy, ethoxy, trifluoromethoxy,trifluoroethoxy or the like), formyl, a C₂₋₄ alkanoyl (for example,acetyl, propionyl or the like), a C₁₋₄ alkylsulfonyl (for example,methanesulfonyl, ethanesulfonyl or the like) and the like, where thenumber of the substituents is preferably 1 to 3.

The substituents for “an amidino group which may be substituted” and “aguanidino group which may be substituted” each of which is representedby R^(e2) are exemplified by substituents similar to those for “an aminogroup which may be substituted, where the nitrogen atom may be convertedinto a quaternary ammonium or the N-oxide” which is represented byR^(e2).

It is preferable that R^(e2) is (1) an amino group which may besubstituted, where the nitrogen atom may be converted into a quaternaryammonium or the N-oxide, (2) a nitrogen-containing heterocyclic ringgroup which may be substituted and may contain the sulfur atom or theoxygen atom as a ring-constituting atom, where the nitrogen atom may beconverted into a quaternary ammonium or the N-oxide, (3) an amidinogroup which may be substituted or (4) a guanidino group which may besubstituted and it is more preferable that R^(e2) is an amino groupwhich may be substituted, where the nitrogen atom may be converted intoa quaternary ammonium or the N-oxide, or the like. Also, R^(e2) may bean amidino group which may be substituted or a guanidino group which maybe substituted.

It is more preferable that R^(e2) is a group represented by—NR^(e)R^(e)″ or —N⁺R^(e)R^(e)′R^(e)″ (wherein each of R^(e), R^(e)′ andR^(e)″ represents an aliphatic hydrocarbon group (an aliphatic-chainhydrocarbon group and an aliphatic, cyclic hydrocarbon group) which maybe substituted or an alicyclic (non-aromatic) heterocyclic ring groupwhich may be substituted).

In the above-mentioned formula, “an aliphatic hydrocarbon group whichmay be substituted” and “an alicyclic heterocyclic ring group which maybe substituted”, which are representd by R^(e), R^(e)′ and R^(e″), areexemplified by substituents similar to “an alicyclic hydrocarbon groupwhich may be substituted (for example, an alkyl, a cycloalkyl, analkenyl, a cycloalkenyl or the like, each of which may be substituted)”and “an alicyclic, heterocyclic ring group which may be substituted (forexample, a 5- to 6-membered non-aromatic heterocyclic ring which may besubstituted or the like)”, which are exemplified by as the substituentswhich may be possessed by “an amino group which may be substituted”representd by R^(e2).

Especially, as for R^(e) and R^(e)′, an aliphatic hydrocarbon groupwhich may be substituted (for example, an alkyl, an alkenyl or the like,each of which may be substituted) is preferable, a C₁₋₆ alkyl groupwhich may be substituted is more preferable and the methyl group whichmay be substituted is particularly preferable.

It is preferable that R^(e)″ is an alicyclic hydrocarbon group which maybe substituted (preferably, a C₃₋₈ cycloalkyl group which may besubstituted; more preferably, a cyclohexyl which may be substituted) oran alicyclic heterocyclic ring group which may be substituted(preferably, a saturated alicyclic heterocyclic ring group which may besubstituted (preferably, a 6-membered cyclic ring group); morepreferably, tetrahydropyranyl which may be substituted,tetrahydrothiopyranyl which may be substituted or piperidyl which may besubstituted; and particularly preferably, tetrahydropyranyl which may besubstituted).

In the above formula (eIa), R^(e1) and Z^(e2) have the same meaningsgiven above.

In the above formula (eIa), a group of the formula:

represented by W^(ea) binds to adjacent groups in the following manner:

In the above formula, examples of the “5- to 6-membered aromatic ring”in the “optionally substituted 5- to 6-membered aromatic ring”represented by A^(ea) include 6-membered aromatic hydrocarbon such asbenzene, etc.; 5- to 6-membered aromatic heterocyclic ring containing 1to 3 hetero-atoms consisting of 1 to 2 kinds of hetero-atoms selectedfrom oxygen atom, sulfur atom and nitrogen atom such as furan,thiophene, pyrrole, imidazole, pyrazole, thiazole, oxazole, isothiazole,isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, triazole, etc.;etc. Among others, benzene, furan, thiophene, pyridine (preferably,6-membered ring) etc. are preferable, and in particular benzene ispreferable.

Examples of the “substituents”, which the “5- to 6-membered aromaticring” in the “optionally substituted 5-to 6-membered aromatic ring”represented by A^(ea) may have, are similar to the “substituents” whichthe “5- to 6-membered ring” in the “optionally substituted 5- to6-membered ring” represented by R^(e1) may have The number of saidsubstituents for the ring A^(ea) is 1-4 (preferably 1-2), and they maybe same or different and present at any possible position (e.g. theposition of the group X^(ea) and the other positions) on the ringrepresented by A^(ea).

In the above formula, examples of the “5- to 7-membered ring” in the“optionally substituted 5- to 7-membered ring” represented by B^(e)include a 5- to 7-membered ring group of the formula:

which may have a substituent at optional, substitutable positions, etc.

In the above formula, Y^(e) has the meaning given above. One to four(preferably one or two) of these substituents for A^(ea) may be the sameor different from each other and present at any positions in the ring,and it is preferable that the carbon atom at the position ea in thegroup:

represented by W^(ea) is not substituted.

In the above formula (eIa), the amino group that may be substituted,where the nitrogen atom may be converted into a quaternary ammonium,represented by R^(e2a) include those mentioned as the amino group thatmay be substituted, where the nitrogen atom may be converted into aquaternary ammonium, represented by R^(e2).

In the above formula (eIa), the group represented by the formularepresented by R^(e2a):

(wherein ek represents 0 or 1, the phosphorus atom may form aphosphonium salt when ek is 0, and each of R^(e5) and R^(e6) representsthe hydrocarbon atom that may be substituted or an amino group that maybe substituted and R^(e5) and R^(e6) may bind each other to form acyclic ring group together with the adjacent phosphorus atom),“hydrocarbon atom that may be substituted” or “an amino group that maybe substituted”represented by R^(e5) or R^(e6) and a cyclic group incase of forming a cyclic ring group by combining R^(e5) and R^(e6)together with the adjacent phosphorus atom include those mentioned asexamples for the above R^(e5′) and R^(e6′).

In the above formula, a counter anion in case that the phosphorus atomis converted into a quaternary ammonium, is exemplified by, in additionto an anion of a halogen atom (for example, Cl⁻, Br⁻, I⁻ or the like) orthe like, an anion derived from an inorganic acid such as hydrochloricacid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid andthe like, an anion derived from an organic acid such as formic acid,acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaricacid, maleic acid, citric acid, succinic acid, malic acid,methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid andthe like and an anion derived from an acidic amino acid such as asparticacid, glutamic acid and the like, where Cl⁻, Br⁻, I⁻ or the like is morepreferable.

As the R^(e2a), “an amino group that may be substituted, where thenitrogen atom may be converted into a quaternary ammonium and the grouprepresented by the formula:—N⁺R^(e)R^(e)′R^(e)″wherein each of R^(e), R^(e)′ and R^(e)″ is an aliphatic hydrocarbongroup which may be substituted or an alicyclic heterocyclic group whichmay be substituted are more preferable.

As an compound of the formula (eIa), a compound of the formula:

wherein R^(e1a) is an optionally substituted phenyl group or anoptionally substituted thienyl group; Y^(e)″ is —CH₂—, —O—, or —S—; andR^(e), R^(e′) and R^(e″) are independently an optionally substitutedaliphatic hydrocarbon group or an optionally substituted alicyclicheterocyclic ring group, is preferable.

In the above formula, the “substituent” which may be possessed by the“phenyl group” in the “optionally substituted phenyl group” and the“thienyl group” in the “potionally substituted thienyl group”, each ofwhich is represented by R^(e1a), include those for the optionallysubstituted 5- or 6-membered cyclic ring group represented by the aboveR^(e1).

Examples of the “optionally substituted aliphatic hydrocarbon group” andthe “optionally substituted alicyclic heterocyclic ring group”represented by R^(e), R^(e)′ or R^(e)″ include those exemplified by thesubstituents for the “optionally substituted amino group” represented byR^(e2a). Among them, as the group R^(e) or R^(e)′, an optionallysubstituted chain hydrocarbon group is preferable, an optionallysubstituted C₁₋₆ alkyl group is more preferable, and an optionallysubstituted methyl group is most preferable; and as the group R″, anoptionally substituted alicyclic hydrocarbon group (more preferably, anoptionally substituted C₃₋₈ cycloalkyl group; more preferably, anoptionally substituted cyclohexyl) or an optionally substitutedalicyclic heterocyclic ring group (preferably, an optionally substitutedsaturated alicyclic heterocyclic ring group (preferably 6-membered ringgroup); more preferably, an optionally substituted tetrahydropyranyl, anoptionally substituted tetrahydrothiopyranyl or an optionallysubstituted piperidyl; most preferably, an optionally substitutedtetrahydropyranyl) is preferable. Furthermore, a compound of theformula:

wherein X^(ea−) is an anion is preferable.

In the above formula, examples of the anion represented by X^(ea−)include an anion of a halogen atom; an anion derived from an inorganicacid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuricacid, phosphoric acid, etc.; an anion derived from an organic acid suchas formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalicacid, tartaric acid, maleic acid, citric acid, succinic acid, malicacid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonicacid, etc.; an anion derived from an acidic amino acid such as asparticacid, glutamic acid, etc.; etc. Among them, an anion of a halogen atomis preferable.

In the above formula (eIb), the substituents of “phenyl group” in the“phenyl group which may be substituted” and the substituents of “thienylgroup” in the “thienyl group which may be substituted” shown by R^(e1b)include those mentioned as the substituents in “5- to 6-membered cyclicring group” shown by R^(e1).

In the above formula (eIb), Y^(eb) is —CH₂—, —O— or —S—; and preferably—CH₂— or —O—.

In the above formula (eIb), R^(e2b), R^(e3b) and R^(e4b) areindependently an “optionally substituted aliphatic hydrocarbon group” oran “optionally substituted alicyclic heterocyclic ring group”.

Examples of the “aliphatic hydrocarbon group” in the “optionallysubstituted aliphatic hydrocarbon group” represented by R^(e2b), R^(e3b)and R^(e4b) include

(1) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably C₁₋₆ alkyl, etc.);

(2) an optionally substituted cycloalkyl (e.g. C₃₋₈ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, etc.);

(3) an optionally substituted alkenyl (e.g. alkenyl which has a carbonnumber of 2 to 10 such as allyl, crotyl, 2-pentenyl, 3-hexenyl, etc.,preferably C₂₋₆alkenyl, etc.);

(4) an optionally substituted cycloalkenyl (e.g. cycloalkenyl which hasa carbon number 3 to 7, such as 2-cyclopentenyl, 2-cyclohexenyl,2-cyclopentenylmethyl, 2-cyclohexenylmethyl, etc.); etc.

Examples of the “alicyclic heterocyclic ring group” in the “optionallysubstituted alicyclic heterocyclic ring group” represented by R^(e2b),R^(e3b) and R^(e4b) include group formed by removing a hydrogen atomfrom a 5- to 6-membered non-aromatic heterocyclic ring containing 1 to 4hetero-atoms consisting of 1 to 2 kinds of hetero-atoms selected fromnitrogen atom, sulfur atom and oxygen atom such as tetrahydrofuran,tetrahydrothiophene, dithiolane, oxathiolane, pyrrolidine, pyrroline,imidazolidine, imidazoline, pyrazolidine, pyrazoline, piperidine,piperazine, oxazine, oxadiazine, thiazine, thiadiazine, morpholine,thiomorpholine, pyran, tetrahydropyran, etc.; preferably a group formedby removing a hydrogen atom from a 5- to 6-membered saturatedheterocyclic ring, containing 1 hetero-atom such as tetrahydrofuran,piperidine, tetrahydropyran, tetrahydrothiopyran, etc.); etc.

Examples of the substituents, which the “aliphatic hydrocarbon group”and the “alicyclic heterocyclic ring group” in the “optionallysubstituted aliphatic hydrocarbon group” and the “optionally substitutedalicyclic heterocyclic ring group” represented by R^(e2b), R^(e3b) andR^(e4b) may have, include halogen (e.g. fluorine, chlorine, bromine,iodine, etc.), an optionally halogenated C₁₋₄ alkyl, an optionallyhalogenated C₁₋₄ alkoxy (e.g. methoxy, ethoxy, trifluoromethoxy,trifluoroethoxy, etc.), C₂₋₄ alkanoyl (e.g. acetyl, propionyl, etc.),C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.), phenyl,phenyl-C₁₋₄ alkyl, C₃₋₇ cycloalkyl, cyano, nitro, oxo, hydroxy mercapto,amino, carboxyl, C₁₋₄ alkoxy-carbonyl (preferably, halogen, anoptionally halogenated C₁₋₄ alkyl, an optionally halogenated C₁₋₄alkoxy, phenyl-C₁₋₄ alkyl, C₃₋₇ cycloalkyl, cyano, oxo, hydroxy group,etc.), etc., and the number of the substituents are preferably 1 to 3.

In the above formula (eIb), as the group R^(e2b) or R^(e3b), anoptionally substituted chain hydrocarbon group is preferable, and anoptionally substituted alkyl group is more preferable. In particular,the groups R^(e2b) and R^(e3b) are preferably the same and morepreferably both of the groups. R^(e2b) and R^(e3b) are methyl.

In the above formula (eIb), as the group R^(e4b), an optionallysubstituted alicyclic hydrocarbon group or an optionally substitutedalicyclic heterocyclic group is preferable and an optionally substitutedcycloalkyl group or an optionally substituted saturated alicyclicheterocyclic ring group is more preferable. In particular, R^(e4b) ispreferably an optionally substituted cyclohexyl or an optionallysubstituted 6-membered saturated alicyclic heterocyclic ring group andmore preferably an optionally substituted cycloalkyl, an optionallysubstituted tetrahydropyranyl, an optionally substitutedtetrahydrothiopyranyl or an optionally substituted piperidyl.

In the formula (eIc), R^(e1) has the same meaning given above.

In the above formula (eIc), the substituent of the 6- to 7-membered ringin a “6- to 7-membered ring which may be substituted” represented byA^(ec) include those which the “5- to 6-membered ring” in the“optionally substituted 5- to 6-membered ring” represented by R^(e1) mayhave. One to three (preferably one to two) of the substituents of A^(ec)are the same or different each other and may be present at any positionon the ring.

In the group of the formula:

a carbon atom at the position ea is preferably unsubstituted.

Examples of the “optionally substituted 6- to 7-membered ring”represented by A^(ec) include a 6- to 7-membered ring group of theformula:

which may have a substituent at any possible position, etc.

In the above formula, Y^(e) has the same meaning given above.

Examples of the “substituents”, which the “benzene ring” in the“optionally substituted benzene ring” represented by B^(ec) may have,include those for the “5- to 6-membered ring” in the “optionallysubstituted 5- to 6-membered ring” represented by R^(e1), etc. Amongthem, halogen (e.g. fluorine, chlorine, bromine, iodine, etc.), nitro,cyano, hydroxy group, an optionally substituted thiol group (e.g. thiol,C₁₋₄ alkylthio, etc.), an optionally substituted amino group (e.g.amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclicamino such as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc., etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc. are preferable and in particular, halogen, an optionallyhalogenated C₁₋₄ alkyl, an optionally halogenated C₁₋₄ alkoxy, etc. arepreferable. The number of the substituents are preferably 1 to 3.

In the above formula (eIc), n is an integer of 1 or 2 (preferably, 2).

In the above formula (eIc), the divalent group represented by Z^(e2) hasthe same meaning given above. In the above formula (eIc), examples of(1) an optionally substituted amino group in which a nitrogen atom mayform a quaternary ammonium, (2) an optionally substitutednitrogen-containing heterocyclic ring group which may contain a sulfuratom or an oxygen atom as ring constituting atoms and wherein a nitrogenatom may form a quaternary ammonium, (3) a group binding through asulfur atom and (4) a group of the formula:

wherein each symbols has the same meanings given above, represented byR^(e2c) are the same as those of R^(e2) mentioned above.

In the above formula (eId), examples of the “5- to 6-membered aromaticring” of the “5- to 6-membered aromatic ring which has a group of theformula: R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- wherein R^(ed) is a hydrogenatom or an optionally substituted hydrocarbon group, X^(ed) is anoptionally substituted alkylene chain, and Z^(e1d) and Z^(e2d) arerespectively heteroatoms, include a 6-membered aromatic hydrocarbon suchas benzene, etc.; 5- to 6-membered aromatic heterocyclic ring containing1 to 4 hetero-atoms consisting of 1 to 2 kinds of hetero-atoms selectedfrom nitrogen atom, sulfur atom and oxygen atom such as furan,thiophene, pyrrole, imidazole, pyrazole, thiazole, oxazole, isothiazole,isoxazole, tetrazole, pyridine, pyrazine, pyrimidine, pyridazine,triazole, etc.; etc. Among them, benzene, furan, thiophene, pyridine,etc. are preferable, benzene, furan or thiophene is more preferable, andin particular, benzene is preferable.

Examples of the “hydrocarbon group” in the “optionally substitutedhydrocarbon group” represented by R^(ed) include

(1) alkyl (e.g. C₁₋₁₀ alkyl such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl,hexyl, heptyl, octyl, nonyl, decyl, etc., preferably lower (C₁₋₆) alkyl,etc., more preferably lower (C₁₋₄) alkyl, etc.);

(2) cycloalkyl (e.g. C₃₋₇ cycloalkyl, etc. such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.);

(3) alkenyl (e.g. alkenyl which has a carbon number of 2 to 10 such asallyl, crotyl, 2-pentenyl, 3-hexenyl, etc., preferably lower (C₂₋₆)alkenyl, etc.);

(4) cycloalkenyl (e.g. cycloalkenyl which has a carbon number of 3 to 7,etc. such as 2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl, etc.);

(5) alkynyl (e.g. alkynyl which has a carbon number of 2 to 10 such asethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-pentynyl, 3-hexynyl, etc.,preferably lower (C₂₋₆) alkynyl, etc.);

(6) aralkyl (e.g. phenyl-C₁₋₁₄ alkyl (e.g. benzyl, phenethyl, etc.),etc.);

(7) aryl (e.g. phenyl, naphthyl, etc.);

(8) cycloalkyl-alkyl (e.g. C₃₋₇ cycloalkyl-C₁₋₄ alkyl such ascyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl,cyclohexylmethyl, cycloheptylmethyl), etc.

Examples of the substituents, which the above-mentioned (1) alkyl, (2)cycloalkyl, (3) alkenyl, (4) cycloalkenyl, (5) alkynyl, (6) aralkyl, (7)aryl and (8) cycloalkyl-alkyl may have, include halogen (e.g. fluorine,chlorine, bromine, iodine, etc.), nitro, cyano, hydroxy group, anoptionally substituted thiol group (e.g., thiol, C₁₋₄ alkylthio, etc.),an optionally substituted amino group (e.g., amino, mono-C₁₋₄alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc., etc.), an optionally esterified or amidatedcarboxyl group (e.g. carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl,mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄ alkylcarbamoyl, etc.), an optionallyhalogenated C₁₋₄ alkyl (e.g. trifluoromethyl, methyl, ethyl, etc.), anoptionally halogenated C₁₋₄ alkoxy (e.g. methoxy, ethoxy, propoxy,butoxy, trifluoromethoxy, trifluoroethoxy, etc.), C₁₋₄ alkylenedioxy(e.g. —O—CH₂—O—, —O—CH₂—CH₂—O—, etc.), an optionally substitutedsulfonamide [a group formed by combining an optionally substituted aminogroup (e.g. amino, a mono-C₁₋₄ alkyklamino, di-C₁₋₄ alkylamino, 5- to6-membered cyclic amino such as tetrahydropyrrole, piperazine,piperidine, morpholine, thiomorpholine, pyrrole, imidazole, etc.) with—SO₂—, etc.], formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl, etc.), C₁₋₄alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.), anoptionally substituted heterocyclic group etc., and the number of thesubstituents are preferably 1 to 3.

The “heterocyclic group” in the “optionally substituted heterocyclicgroup” which is the substituent for the “optionally substitutedhydrocarbon group”represented by R^(ed) is exemplified by a group whichis formed by removing one hydrogen atom from an aromatic heterocyclicring or non-aromatic heterocyclic ring. The aromatic heterocyclic ringinclude a 5- to 6-membered aromatic heterocyclic ring, which contains 1to 4 hetero atoms of 1 to 2 kinds selected from the nitrogen atom, thesulfur atom and the oxygen atom, such as furan, thiophene, pyrrole,imidazole, pyrazole, thiazole, oxazole, isothiazole, isoxazole,tetrazole, pyridine, pyrazine, pyrimidine, pyridazine, triazole,oxadiazole, thiadiazole or the like, and the non-aromatic heterocyclicring includes a 5- to 6-membered non-aromatic heterocyclic ring, whichcontains 1 to 4 heteroatoms of 1 to 2 kinds selected from the nitrogenatom, the sulfur atom and the oxygen atom, such as tetrahydrofuran,tetrahydrothiophene, dioxolan dithiolan, oxathiolan, pyrrolidine,pyrroline, imidazolidine, imidazoline, pyrazolidine, pyrazoline,piperidine, piperazine, oxazine, oxadiazine, thiazine, thiadiazine,morpholine, thiomorpholine, pyran, tetrahydropyran or the like andnon-aromatic heterocyclic ring group formed by being saturated all or apart of the bond of the ring (preferably, aromatic heterocyclic ringsuch as pyrazole, thiazole, oxazole tetrazole or the like).

Examples of “heterocyclic ring” of “heterocyclic group which may besubstituted” which is the substituent of the “optionally substitutedhydrocarbon group” represented by R^(ed), may optionally have 1 to 3substituents at any substitutable position. The substituent include ahalogen atom (e.g. fluorine, chlorine, bromine, iodine, et.), nitro,cyano, hydroxyl, a thiol group which may be substituted (e.g. thiol, aC₁₋₄ alkylthio, etc.), an amino group which may be substituted (e.g.amino, a mono-C₁₋₄ alkylamino, a di-C₁₋₄ alkylamino, a 5- to 6-memberedcyclic amino such as tetrahydropyrrole, piperazine, piperidine,morpholine, thiomorpholine, pyrrole, imidazole, etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), C₁₋₄ alkylenedioxy (e.g. —O—CH₂—O—,—O—CH₂—CH₂—O—, etc.), an optionally substituted sulfonamide [a groupformed by combining an optionally substituted amino group (e.g. amino, amonoC₁₋₄ alkyklamino, diC₁₋₄ alkylamino, 5- to 6-membered cyclic aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc.) with —SO₂—, etc.], formyl,C₂₋₄ alkanoyl (e.g. acetyl, propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g.methanesulfonyl, ethanesulfonyl, etc.), (preferably C₁₋₄ alkyl etc.)

When the group of the formula: R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- (whereineach symbol has the same meaning given above) is a monovalent group, (itdoes not bind to the 5- to 6-membered aromatic ring to form a ring), anoptionally substituted alkyl group is preferable as the group R^(ed), anoptionally halogenated lower alkyl group is more preferable, and inparticular, an optionally halogenated C₁₋₄ alkyl group is preferable.

In the above formula (eId), examples of the “optionally substitutedalkylene chain” represented by X^(ed) include an optionally substitutedstraight or branched C₁₋₆ alkylene, etc. In said alkylene chain, astraight portion is preferably constituted by 1-4 carbon atoms, and inparticular, an optionally substituted straight C₁₋₄ alkylene (preferablyethylene or propylene) is preferable as X^(ed).

Examples of the substituent, which the “alkylene chain” in the“optionally substituted alkylene chain” represented by X^(ed) may have,include any one of which can bind to a divalent chain constituting thestraight portion, for example, lower alkyl which has a carbon number of1 to 6 (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, etc.), lower(C₃₋₇) cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, etc.), formyl, lower (C₂₋₇) alkanoyl (e.g.acetyl, propionyl, butyryl, etc.), an optionally esterified phosphonogroup, an optionally esterified carboxyl group, hydroxy group, oxo,etc., and more preferably lower alkyl which has a carbon number of 1 to6 (preferably C₁₋₃ alkyl), hydroxy group, oxo, etc.

Examples of the optionally esterified phosphono group include a group ofthe formula: P(O) (OR^(e7d)) (OR^(e8d)) wherein R^(e7d) and R^(e8d) areindependently hydrogen, a alkyl group which has a carbon number of 1 to6 or a cycloalkyl group which has a carbon number of 3 to 7, and R^(e7d)and R^(e8d) may bind to each other to form a 5- to 7-membered ring.

In the above formula, examples of the alkyl group which has a carbonnumber of 1 to 6 represented by R^(e7d) and R^(e8d) include methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, etc., and examples of thecycloalkyl which has a carbon number of 3 to 7 include cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc. Among them, astraight-chain lower alkyl which has a carbon number of 1 to 6 ispreferable and lower alkyl which has a carbon number of 1 to 3 is morepreferable. The groups R^(e7d) and R^(e8d) may be same or different, andpreferably the groups R^(e7d) and R^(e8d) are same. When R^(e7d) andR^(e8d) may bind to each other to form a 5- to 7-membered ring, thegroups R^(e7d) and R^(e8d) bind to each other to represent astraight-chain C₂₋₄ alkylene side chain of the formula: —(CH₂)₂—,—(CH₂)₃—, —(CH₂)₄—, etc. Said side chain may have a substituent, andexamples of the substituent include hydroxy group, halogen, etc.

Examples of the optionally esterified carboxyl group include an estergroup formed by binding a carboxyl group to an alkyl group which has acarbon number of 1 to 6 or a cycloalkyl group which has a carbon numberof 3 to 7 (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,sec-butoxycarbonyl, tert-butoxy-carbonyl, pentyloxycarbonyl,hexyloxycarbonyl, etc.).

As the group X^(ed), an optionally substituted C₁₋₄ alkylene ispreferable, C₁₋₄ alkylene which may be substituted with C₁₋₃ alkyl,hydroxy group or oxo is more preferable, and in particular, a group ofthe formula: —(CH₂)_(en)— (en is an integer of 1-4) is preferable.

Examples of the hetero-atom represented by Z^(e1d) and Z^(e2d) include—O—, —S(O)_(em)— (em is an integer of 0 to 2), —N(R^(e4d)) (R^(e4d) is ahydrogen atom or an optionally substituted lower alkyl group), etc. Asthe group Z^(e1d), —O— or —S(O)_(em)— (em is an integer of 0 to 2) ispreferable, and —O— is more preferable. As the group Z^(e2d), —O— or—N(R^(e4d))— (R^(e4d) is a hydrogen atom or an optionally substitutedlower alkyl group) is preferable, and —O— is more preferable.

Examples of the optionally substituted lower alkyl group represented byR^(e4d) are similar to the above “optionally substituted lower alkylgroup” exemplified in the “optionally substituted hydrocarbon group”represented by R^(ed).

Examples of the further substituent, which the “5- to 6-membered ring”in the “5- to 6-membered aromatic ring which has a group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- wherein each symbol is the same meaninggiven above, and which may have a further substituent” represented byR^(e1d) may have, in addition to the group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)-, include a halogen atom, nitro, cyano, anoptionally substituted alkyl, an optionally substituted cycloalkyl, anoptionally substituted hydroxy group, an optionally substituted thiolgroup (wherein a sulfur atom may be oxidized to form an optionallysubstituted sulfinyl group or an optionally substituted sulfonyl group),an optionally substituted amino group, an optionally substituted acylgroup, an optionally esterified or amidated carboxyl group, anoptionally substituted aromatic group.

Examples of the halogen as the substituents for R^(e1d) includefluorine, chlorine, bromine, iodine, etc. Among them, fluorine andchlorine are preferable.

Examples of the alkyl in the optionally substituted alkyl as thesubstituents for R^(e1d) include a straight or branched alkyl which hasa carbon number of 1 to 10 such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl,hexyl, heptyl, octyl, nonyl, decyl, etc., and preferably lower (C₁₋₆)alkyl.

Examples of the substituents in the optionally substituted alkyl includehalogen (e.g. fluorine, chlorine, bromine, iodine, etc.), nitro, cyano,hydroxy group, an optionally substituted thiol group (e.g. thiol, C₁₋₄alkylthio, etc.), an optionally substituted amino group (e.g. amino,mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc., etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkoxy (e.g.methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy, trifluoroethoxy,etc.), an optionally halogenated C₁₋₄ alkoxy-C₁₋₄ alkoxy (e.g.methoxymethoxy, methoxyethoxy, ethoxyethoxy, trifluoromethoxyethoxy,trifluoroethoxyethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl,propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl,ethanesulfonyl, etc.), etc., and the number of the substituents arepreferably 1 to 3.

Examples of the cycloalkyl in the optionally substituted cycloalkyl asthe substituents for R^(e1d) include C₃₋₇ cycloalkyl, etc. such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

Examples of the substituents in the optionally substituted cycloalkylinclude halogen (e.g. fluorine, chlorine, bromine, iodine, etc.), nitro,cyano, hydroxy group, an optionally substituted thiol group (e.g. thiol,C₁₋₄ alkylthio, etc.), an optionally substituted amino group (e.g.amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclicamino such as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc., etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), C formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc., and the number of the substituents are preferably 1 to 3.

Examples of the substituents in the optionally substituted hydroxy groupas the substituents for R¹ include

(1) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(2) an optionally substituted cycloalkyl which may contain a hetero-atom(e.g. C₃₋₇ cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, etc.; a saturated 5- to 6-membered heterocyclicring group containing 1 to 2 hetero-atoms such as tetrahydrofuranyl,tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, piperidyl, piperazinyl,morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrothiopyranyl,etc (preferably, tetrahydropyranyl, etc.); etc.);

(3) an optionally substituted alkenyl (e.g. alkenyl which has a carbonnumber of 2 to 10 such as allyl, crotyl, 2-pentenyl, 3-hexenyl, etc.,preferably lower (C₂₋₆)alkenyl, etc.);

(4) an optionally substituted cycloalkenyl (e.g. cycloalkenyl which hasa carbon number of 3 to 7, etc. such as 2-cyclopentenyl, 2-cyclohexenyl,2-cyclopentenylmethyl, 2-cyclohexenylmethyl, etc.);

(5) an optionally substituted aralkyl (e.g. phenyl-C₁₋₄ alkyl (e.g.benzyl, phenethyl, etc.), etc.);

(6) formyl or an optionally substituted acyl (e.g. alkanoyl which has acarbon number of 2 to 4 (e.g. acetyl, propionyl, butyryl, isobutyryl,etc.), alkylsulfonyl which has a carbon number of 1 to 4 (e.g.methanesulfonyl, ethanesulfonyl, etc.), etc.);

(7) an optionally substituted aryl (e.g. phenyl, naphthyl, etc.); etc.

Examples of the substituents which the above-mentioned (1) optionallysubstituted alkyl, (2) optionally substituted cycloalkyl, (3) optionallysubstituted alkenyl, (4) optionally substituted cycloalkenyl, (5)optionally substituted aralkyl, (6) optionally substituted acyl and (7)optionally substituted aryl may have include halogen (e.g., fluorine,chlorine, bromine, iodine, etc.), nitro, cyano, hydroxy group, anoptionally substituted thiol group (e.g., thiol, C₁₋₄ alkylthio, etc.),an optionally substituted amino group (e.g. amino, mono-C₁₋₄ alkylamino,di-C₁₋₄ alkylamino, 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc., etc.), an optionally esterified or amidatedcarboxyl group (e.g. carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl,mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄ alkylcarbamoyl, etc.), an optionallyhalogenated C₁₋₄ alkyl (e.g. trifluoromethyl, methyl, ethyl, etc.), anoptionally halogenated C₁₋₆ alkoxy (e.g. methoxy, ethoxy, propoxy,butoxy, trifluoromethoxy, trifluoroethoxy, etc.; preferably anoptionally halogenated C₁₋₄ alkoxy), formyl, C₂₋₄ alkanoyl (e.g. acetyl,propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl,ethanesulfonyl, etc.), an optionally substituted 5- to 6-memberedaromatic heterocyclic ring [e.g. 5- to 6-membered aromatic heterocyclicring containing 1 to 4 hetero-atoms consisting of 1 to 2 kinds ofhetero-atoms selected from nitrogen atom, sulfur atom and oxygen atomsuch as furan, thiophene, pyrrole, imidazole, pyrazole, thiazole,oxazole, isothiazole, isoxazole, tetrazole, pyridine, pyrazine,pyrimidine, pyridazine, triazole, etc.; Examples of the substituentswhich said heterocyclic ring may have include halogen (e.g. fluorine,chlorine, bromine, iodine, etc.), nitro, cyano, hydroxy group, thiolgroup, amino group, carboxyl group, an optionally halogenated C₁₋₄ alkyl(e.g. trifluoromethyl, methyl, ethyl, etc.), an optionally halogenatedC₁₋₄ alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc., and the number of the substituents are preferably 1 to 3], etc.,and the number of the substituents are preferably 1 to 3.

Examples of the substituents in the optionally substituted thiol groupas the substituents for R^(e1d) are similar to the above-describedsubstituents in the optionally substituted hydroxy group as thesubstituents for R^(e1d), and among them,

(1) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(2) an optionally substituted cycloalkyl (e.g. C₃₋₇ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,etc.);

(3) an optionally substituted aralkyl (e.g. phenyl-C₁₋₄ alkyl (e.g.benzyl, phenethyl, etc.), etc.);

(4) an optionally substituted aryl (e.g. phenyl, naphthyl, etc.); etc.are preferable.

Examples of the substituents which the above-mentioned (1) optionallysubstituted alkyl, (2) optionally substituted cycloalkyl, (3) optionallysubstituted aralkyl and (4) optionally substituted aryl may have includehalogen (e.g., fluorine, chlorine, bromine, iodine, etc.), nitro, cyano,hydroxy group, an optionally substituted thiol group (e.g., thio, C₁₋₄alkylthio, etc.), an optionally substituted amino group (e.g. amino,mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc., etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc., and the number of the substituents are preferably 1 to 3.

Examples of the substituents in the optionally substituted amino groupas the substituents for R^(e1d) include an amino group which may haveone to two substituents similar to the above-described substituents inthe optionally substituted hydroxy group as the substituents forR^(e1d), etc. Among them,

(1) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(2) an optionally substituted cycloalkyl (e.g. C₃₋₇ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,etc.);

(3) an optionally substituted alkenyl (e.g. alkenyl which has a carbonnumber of 2 to 10 such as allyl, crotyl, 2-pentenyl, 3-hexenyl, etc.,preferably lower (C₂₋₆) alkenyl, etc.);

(4) an optionally substituted cycloalkenyl (e.g. cycloalkenyl which hasa carbon number of 3 to 7, etc. such as 2-cyclopentenyl, 2-cyclohexenyl,2-cyclopentenylmethyl, 2-cyclohexenylmethyl, etc.);

(5) formyl or an optionally substituted acyl (e.g. alkanoyl which has acarbon number of 2 to 4 (e.g. acetyl, propionyl, butyryl, isobutyryl,etc.), which has a carbon number of 1 to 4 alkylsulfonyl (e.g.methanesulfonyl, ethanesulfonyl, etc.), etc.);

(6) an optionally substituted aryl (e.g. phenyl, naphthyl, etc.); etc.are preferable.

Examples of the substituents, which each of the above-described (1)optionally substituted alkyl, (2) optionally substituted cycloalkyl, (3)optionally substituted alkenyl, (4) optionally substituted cycloalkenyl,(5) optionally substituted acyl and (6) optionally substituted aryl mayhave, include halogen (e.g. fluorine, chlorine, bromine, iodine, etc.),nitro, cyano, hydroxy group, an optionally substituted thiol group (e.g.thiol, C₁₋₄ alkylthio, etc.), an optionally substituted amino group(e.g. amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-memberedcyclic amino such as tetrahydropyrrole, piperazine, piperidine,morpholine, thiomorpholine, pyrrole, imidazole, etc., etc.), anoptionally esterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc., and the number of the substituents is preferably 1 to 3.

The substituents in the optionally substituted amino group as thesubstituents for R^(e1d) may bind to each other to form a cyclic aminogroup (e.g. 5- to 6-membered cyclic amino, etc. such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc.). Said cyclic amino group may have asubstituent, and examples of the substituents include halogen (e.g.fluorine, chlorine, bromine, iodine, etc.), nitro, cyano, hydroxy group,an optionally substituted thiol group (e.g. thiol, C₁₋₄ alkylthio,etc.), an optionally substituted amino group (e.g. amino, mono-C₁₋₄alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc., etc.), an optionally esterified or amidatedcarboxyl group (e.g. carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl,mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄ alkylcarbamoyl, etc.), an optionallyhalogenated C₁₋₄ alkyl (e.g. trifluoromethyl, methyl, ethyl, etc.), anoptionally halogenated C₁₋₄ alkoxy (e.g. methoxy, ethoxy, propoxy,butoxy, trifluoromethoxy, trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl(e.g. acetyl, propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g.methanesulfonyl, ethanesulfonyl, etc.), etc., and the number of thesubstituents is preferably 1 to 3.

Examples of the optionally substituted acyl as the substituents forR^(e1d) include a carbonyl group or a sulfonyl group binding to

(1) hydrogen;

(2) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(3) an optionally substituted cycloalkyl (e.g. C₃₋₇ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,etc.);

(4) an optionally substituted alkenyl (e.g. alkenyl which has a carbonnumber of 2 to 10 such as allyl, crotyl, 2-pentenyl, 3-hexenyl, etc.,preferably lower (C₂₋₆) alkenyl, etc.);

(5) an optionally substituted cycloalkenyl (e.g. cycloalkenyl which hasa carbon number of 3 to 7, etc. such as 2-cyclopentenyl, 2-cyclohexenyl,2-cyclopentenylmethyl, 2-cyclohexenylmethyl, etc.);

(6) an optionally substituted 5- to 6-membered monocyclic aromatic group(e.g. phenyl, etc., 5- to 6-membeed aromatic heterocyclic groupcontaining 1 to 4 hetero-atoms of 1 to 2 kinds selected from nitrogenatom, sulfur atom and oxygen atom, such as furyl, thienyl, pyrrolyl,imidazole, pyrazolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl,tetrazolyl, pyridyl, pyrazyl, pyrimidyl, pyridazinyl, triazolyl, etc.,preferably, pyridyl, thienyl, etc.)

(7) an optionally substituted 5- to 6-membered monocyclic non-aromaticheterocyclic group (a group formed by removing one hydrogen atom from a5- to 6-membered monocyclic non-aromatic heterocyclic ring whichcontains 1 to 4 heteroatoms of 1 to 2 kinds selected from nitrogen atom,sulfur atom and oxygen atom such as tetrahydrofuran,tetrahydrothiophene, dithiolane, oxathiolane, pyrrolidine, pyrroline,imidazolidine, imidazoline, pyrazolidine, pyrazoline, piperidine,piperazine, oxazine, oxadiazine, thiazine, thiadiazine, morpholine,thiomorpholine, pyran, tetrahydropyran, etc., preferably dioxolanyl,etc.) with carbonyl or sulfonyl group (e.g. acetyl, propionyl, butyryl,isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl,octanoyl, cyclobutanecarbonyl, cyclopentanecarbonyl,cyclohexanecarbonyl, cycloheptanecarbonyl, crotonyl,2-cyclohexenecarbonyl, benzoyl, nicotinoyl, methanesulfonyl,ethanesulfonyl, etc.)

Examples of the substituents, which the above-mentioned (2) optionallysubstituted alkyl, (3) optionally substituted cycloalkyl, (4) optionallysubstituted alkenyl, (5) optionally substituted cycloalkenyl, (6)optionally substituted 5- to 6-membered monocyclic aromatic group and(7) optionally substituted 5- to 6-membered non-aromatic heterocyclicgroup may have, include a halogen (e.g. fluorine, chlorine, bromine,iodine, etc.), nitro, cyano, hydroxyl group, an optionally substitutedthiol group (e.g. thiol, C₁₋₄ alkylthio, etc.), an optionallysubstituted amino group (e.g. amino, mono-C₁₋₄ alkylamino, di-C₁₋₄alkylamino, a 5- to 6-membered cyclic amino such as tetrahydropyrrole,piperazine, piperidine, morpholine, thiomorpholine, pyrrole, imidazole,etc., etc.), an optionally esterified or amidated carboxyl group (e.g.carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl,di-C₁₋₄ alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl(e.g. trifluoromethyl, methyl, ethyl, etc.), an optionally halogenatedC₁₋₄ alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), C₁₋₄ alkylenedioxy (e.g. —O—CH₂—O—,—O—CH₂—CH₂—O—, etc.), an optionally substituted sulfonamide [a groupformed by combining an optionally substituted amino group (e.g. amino, amonoC₁₋₄ alkyklamino, diC₁₋₄ alkylamino, 5- to 6-membered cyclic aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc.) with —SO₂—, etc.], formyl, aC₂₋₄ alkanoyl (e.g. acetyl, propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g.methanesulfonyl, ethanesulfonyl, etc.), etc., and the number of thesubstituents are preferably 1 to 3.

Examples of the optionally esterified carboxyl group as the substituentsfor R^(e1d) include a carbonyloxy group binding to

(1) hydrogen;

(2) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(3) an optionally substituted cycloalkyl (e.g. C₃₋₇ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,etc.);

(4) an optionally substituted alkenyl (e.g. alkenyl which has a carbonnumber of 2 to 10 such as allyl, crotyl, 2-pentenyl, 3-hexenyl, etc.,preferably lower (C₂₋₆) alkenyl, etc.);

(5) an optionally substituted cycloalkenyl (e.g. cycloalkenyl which hasa carbon number of 2 to 1, etc. such as 2-cyclopentenyl, 2-cyclohexenyl,2-cyclopentenylmethyl, 2-cyclohexenylmethyl, etc.);

(6) an optionally substituted aryl (e.g. phenyl, naphthyl, etc.); etc.,and preferably carboxyl, lower (C₁₋₆) alkoxycarbonyl, aryloxycarbonyl(e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, phenoxycarbonyl,naphthoxycarbonyl, etc.), etc.

Examples of the substituents, which the above-mentioned (2) optionallysubstituted alkyl, (3) optionally substituted cycloalkyl, (4) optionallysubstituted alkenyl, (5) optionally substituted cycloalkenyl and (6)optionally substituted aryl may have, include halogen (e.g. fluorine,chlorine, bromine, iodine, etc.), nitro, cyano, hydroxy group, anoptionally substituted thiol group (e.g. thiol, C₁₋₄ alkylthio, etc.),an optionally substituted amino group (e.g. amino, mono-C₁₋₄ alkylamino,di-C₁₋₄ alkylamino, 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc., etc.), an optionally esterified or amidatedcarboxyl group (e.g. carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl,mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄ alkylcarbamoyl, etc.), an optionallyhalogenated C₁₋₄ alkyl (e.g. trifluoromethyl, methyl, ethyl, etc.), anoptionally halogenated C₁₋₄ alkoxy (e.g. methoxy, ethoxy, propoxy,butoxy, trifluoromethoxy, trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl(e.g. acetyl, propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g.methanesulfonyl, ethanesulfonyl, etc.), etc., and the number of thesubstituents are preferably 1 to 3.

Examples of the optionally amidated carboxyl group as the substituentsfor R^(e1d) include an carbonyl group binding to an optionallysubstituted amino group, etc. which is similar to the above-described“optionally substituted amino group as the substituents for R^(e1d)”,and among others, carbamoyl, mono-C₁₋₆ alkylcarbamoyl, di-C₁₋₆alkylcarbamoyl, etc. are preferable.

Examples of the aromatic group in the optionally substituted aromaticgroup as the substituents for R^(e1d) include 5- to 6-membered aromatichomocyclic or heterocyclic ring such as phenyl, pyridyl, furyl, thienyl,pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isothiazolyl,isoxazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazolyl,oxadiazolyl, thiadiazolyl, etc.; fused aromatic heterocyclic ring suchas benzofuran, indole, benzothiophene, benzoxazole, benzothiazole,indazole, benzimidazole, quinoline, isoquinoline, quinoxaline,phthalazine, quinazoline, cinnoline, etc.; etc.

Examples of the substituents for these aromatic groups include halogen(e.g. fluorine, chlorine, bromine, iodine, etc.), nitro, cyano, hydroxygroup, an optionally substituted thiol group (e.g. thiol, C₁₋₄alkylthio, etc.), an optionally substituted amino group (e.g. amino,mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic aminosuch as tetrahydropyrrole, piperazine, piperidine, morpholine,thiomorpholine, pyrrole, imidazole, etc., etc.), an optionallyesterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), an optionally halogenated C₁₋₄ alkyl (e.g.trifluoromethyl, methyl, ethyl, etc.), an optionally halogenated C₁₋₄alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), formyl, C₂₋₄ alkanoyl (e.g. acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g. methanesulfonyl, ethanesulfonyl, etc.),etc., and the number of the substituents is preferably 1 to 3.

The number of the above-mentioned substituents for R1 is 1-4 (preferably1 to 2) and they may be same or different and present at any possibleposition on the ring.

When the group represented by R^(ed) binds to the 5 to 6 memberedaromatic ring to form a ring, the group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- wherein each symbol is as defined above(as the group R^(ed) is preferably a hydrogen atom) forms a divalentgroup such as lower (C₁₋₆) alkylenedioxy (e.g., —O—CH₂—O—,—O—CH₂—CH₂—O—, —O—CH₂—CH₂—CH₂—O—, etc.), oxy-lower (C₁₋₆) alkylene-amino(e.g., —O—CH₂—NH—, —O—CH₂—CH₂—NH—, etc.), oxy-lower (C₁₋₆) alkylenethio(e.g., —O—CH₂—S—, —O—CH₂—CH₂—S—, etc.), lower (C₁₋₆) alkylene-diamino(e.g., —NH—CH₂—NH—, —NH—CH₂—CH₂—NH—, etc.), thia-lower (C₁₋₆)alkylene-amino (e.g., —S—CH₂—NH—, —S—CH₂—CH₂—NH—, etc.), etc. Examplesof the further substituent, which the “5 to 6 membered ring” in the “5to 6 membered aromatic ring which has a group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- wherein each symbol is as defined above,and which may have a further substituent” represented by R^(e1d) mayhave, in addition to the group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)- include a lower (C₁₋₄) alkyl optionallysubstituted with a halogen or a lower (C₁₋₄) alkoxy (e.g. methyl, ethyl,t-butyl, trifluoromethyl, methoxymethyl, ethoxymethyl, propoxymethyl,butoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, butoxyethyl,etc.), a lower (C₁₋₄) alkoxy optionally substituted with a halogen or alower (C₁₋₄) alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, t-butoxy,trifluoromethoxy, methoxymethoxy, ethoxymethoxy, propoxymethoxy,butoxymethoxy, methoxyethoxy, ethoxyethoxy, propoxyethoxy, butoxyethoxy,methoxypropoxy, ethoxypropoxy, propoxypropoxy, butoxypropoxy, etc.),halogen (e.g. fluorine, chlorine, etc.), nitro, cyano, an aminooptionally substituted with 1-2 lower (C₁₋₄) alkyl, formyl or lower(C₂₋₄) alkanoyl (e.g. amino, methylamino, dimethylamino, formylamino,acetylamino, etc.), 5- to 6-membered cyclic amino (e.g. 1-pyrrolidinyl,1-piperazinyl, 1-piperidinyl, 4-morpholino, 4-thiomorpholino,1-imidazolyl, 4-tetrahydropyranyl, etc.), etc.

When R^(e1d) is a benzene, the “group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)-” is preferably present at para positionand the further substituent, which the “5 to 6 membered aromatic ringwhich may have, in addition to the group of the formula:R^(ed)-Z^(e1d)-X^(ed)-Z^(e2d)-, is preferably present at meta position.

In the above formula, examples of the “optionally substituted iminogroup” represented by Y^(ed) include a divalent group of the formula:—N(R^(e5d))- wherein R^(e5d) is a hydrogen atom or a substituent, etc.

As R^(e5d), a hydrogen atom, an optionally substituted hydrocarbongroup, an optionally substituted heterocyclic group, an optionallysubstituted hydroxyl group, an optionally substituted thiol group (whichmay be oxidized, and form an optionally substituted sulfinyl group or anoptionally substituted sulfonyl group), an optionally substituted aminogroup, an optionally esterified or amidated carboxyl group, and anoptionally substituted acyl group etc., are preferable, and a hydrogenatom, an optionally substituted hydrocarbon group, an optionallysubstituted heterocyclic group, an optionally substituted acyl group,etc. are more preferable. Preferable examples of R^(e5d) include ahydrogen atom, an optionally substituted hydrocarbon group, anoptionally substituted acyl group, etc., and C₁₋₄ alkyl, C₁₋₄alkylsulfonyl, formyl, C₂₋₅ alkanoyl, etc. are more preferable, C₁₋₄alkyl, formyl, C₂₋₅ alkanoyl, etc. are further more preferable, and inparticular, formyl or ethyl is preferable. As examples of preferableembodiment of R^(ed), a group represented by the formula:—(CH₂)_(ek)—R^(e6d), wherein ek is 0 or 1, and R^(e6d) represents anoptionally substituted 5- to 6-membered monocyclic aromatic group (forexample, those similar to “(6) an optionally substituted 5- to6-membered monocyclic aromatic group” mentioned in the item “anoptionally substituted acyl group” as the substitutent of R^(ed) arementioned, and phenyl, pyrazolyl, thiazolyl, oxazolyl, tetrazolyl, eachof which may be substituted by a halogen, an optionally halogenated C₁₋₄alkyl, an optionally halogenated C₁₋₄ alkoxy, etc., etc. arepreferable.).

Specific examples of the “optionally substituted hydrocarbon group” asR^(e5d) are similar to the “optionally substituted hydrocarbon group” asR^(ed). Specific examples of the “optionally substituted heterocyclicgroup” as R^(ed) are similar to the “optionally substituted heterocyclicgroup” which is a substituent of the “optionally substituted hydrocarbongroup” represented by R^(ed). Specific examples of the “optionallysubstituted hydroxyl group”, the “optionally substituted thiol group,the “optionally substituted amino group”, the “optionally esterified oramidated carboxyl group” and the “optionally substituted acyl group”,each of which is represented by R^(e5d), are similar to the “optionallysubstituted hydroxyl group”, the “optionally substituted thiol group”,the “optionally substituted amino group”, the “optionally esterified oramidated carboxyl group” and the “optionally substituted acyl group”,each of which is the substituent of R^(e1d), respectively.

In the above formula (eId), examples of the “optionally substitutedaliphatic hydrocarbon group” (aliphatic chain hydrocarbon group andaliphatic cyclic hydrocarbon group) represented by R^(e2d) and R^(e3d)include

(1) an optionally substituted alkyl (e.g. C₁₋₁₀ alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.,preferably lower (C₁₋₆) alkyl, etc.);

(2) an optionally substituted cycloalkyl (e.g. C₃₋₈ cycloalkyl, etc.such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, etc.), provided that

(2-1) said cycloalkyl may contain one hetero-atom selected from a sulfuratom, an oxygen atom and a nitrogen atom to form oxirane, thiorane,aziridine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine,tetrahydropyran, tetrahydrothiopyran, tetrahydrothiopyran 1-oxide,piperidine, etc. (preferably, 6-membered ring such as tetrahydropyran,tetrahydrothiopyran, piperidine, etc.); that

(2-2) said cycloalkyl may be fused with a benzene ring to form indane,tetrahydronaphthalene, etc. (preferably, indane, etc.); and that

(2-3) said cycloalkyl may be clrosslinked via straight-chained, atomchain having a carbon number of 1 to 2, and may form a crosslinkedcyclic hydrocarbon residue such as bicyclo[2.2.1]heptyl,bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, etc.,preferably, a cyclohexyl group, etc. having a bridging comprising astraight chain constituted by 1-2 carbon atoms, and more preferablybicyclo[2.2.1]heptyl, etc.;

(3) an optionally substituted alkenyl (e.g. C₂₋₁₀ alkenyl such as allyl,crotyl, 2-pentenyl, 3-hexenyl, etc., preferably lower (C₂₋₆)alkenyl,etc.);

(4) an optionally substituted cycloalkenyl (e.g. C₃₋₇ cycloalkenyl, etc.such as 2-cyclopentenyl, 2-cyclohexenyl, 2-cyclopentenylmethyl,2-cyclohexenylmethyl, etc.); etc.

Examples of the substituents, which the above-mentioned (1) optionallysubstituted alkyl, (2) optionally substituted cycloalkyl, (3) optionallysubstituted alkenyl and (4) optionally substituted cycloalkenyl mayhave, include halogen (e.g. fluorine, chlorine, bromine, iodine, etc.),an optionally halogenated lower (C₁₋₄) alkyl, an optionally halogenatedC₁₋₄ alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, trifluoromethoxy,trifluoroethoxy, etc.), C₁₋₄ alkylenedioxy (e.g., —O—CH₂—O—,—O—CH₂—CH₂—O—, etc.), formyl, C₂₋₄ alkanoyl (e.g., acetyl, propionyl,etc.), C₁₋₄ alkylsulfonyl (e.g., methanesulfonyl, ethanesulfonyl, etc.),phenyl-lower (C₁₋₄) alkyl, C₃₋₇ cycloalkyl, cyano, nitro, hydroxy group,an optionally substituted thiol group (e.g. thiol, C₁₋₄ alkylthio,etc.), an optionally substituted amino group (e.g. amino, mono-C₁₋₄alkylamino, di-C₁₋₄ alkylamino, 5- to 6-membered cyclic amino such astetrahydropyrrole, piperazine, piperidine, morpholine, thiomorpholine,pyrrole, imidazole, etc., etc.), an optionally esterified or amidatedcarboxyl group (e.g. carboxyl, C₁₋₄ alkoxy-carbonyl, carbamoyl,mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄ alkylcarbamoyl, etc.), a lower (C₁₋₄)alkoxy-carbonyl, oxo group (preferably, halogen, an optionallyhalogenated lower (C₁₋₄) alkyl, an optionally halogenated lower (C₁₋₄)alkoxy, phenyl-lower (C₁₋₄) alkyl, C₃₋₇ cycloalkyl, cyano, hydroxygroup, etc.), etc., and the number of the substituents are preferably 1to 3 examples of the “optionally substituted aliphatic hydrocarbongroup” represented by R^(e2d) and R^(e3d) include

(1) a lower (C₁₋₆) straight or branched alkyl which may have 1-3substituents selected from the class consisting of halogen, cyano,hydroxy group and C₃₋₇ cycloalkyl;

(2) C₅₋₈ cycloalkyl which may be substituted with 1-3 substituentsselected from the class consisting of a halogen, an optionallyhalogenated lower (C₁₋₄) alkyl and a phenyl-lower (C₁₋₄) alkyl, whichmay contain a hetero-atom selected from the class consisting of a sulfuratom, an oxygen atom and a nitrogen atom, which may be fused with abenzene ring and which may be crosslinked via straight-chained, atomchain having the carbon number of 1 to 2 (e.g., cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, tetrahydropyranyl, tetrahydrothiapyranyl,piperidinyl, indanyl, tetrahydronaphthalenyl, bicyclo[2.2.1]heptyl,etc., each of which may be substituted); etc.

In the above formula (eId), examples of the “optionally substitutedalicyclic (non-aromatic) heterocyclic group” represented by R^(e2d) andR^(e3d) include 5- to 6-membered non-aromatic heterocyclic ringcontaining 1 to 4 hetero-atoms consisting of 1 to 2 kinds ofhetero-atoms selected from nitrogen atom, sulfur atom and oxygen atomsuch as tetrahydrofuran, tetrahydrothiophene, dioxolane, dithiolane,oxathiolane, pyrrolidine, pyrroline, imidazolidine, imidazoline,pyrazolidine, pyrazoline, piperidine, piperazine, oxazine, oxadiazine,thiazine, thiadiazine, morpholine, thiomorpholine, pyran,tetrahydropyran, tetrahydrothiopyran, etc., preferably, a 5- to6-membered non-aromatic heterocyclic ring containing 1 hetero-atom suchas tetrahydrofuran, piperidine, tetrahydropyran, etc. or the like.

Examples of the substituent, which the “alicyclic heterocyclic group” inthe “optionally substituted alicyclic heterocyclic group” represented byR^(e2d) and R^(e3d) may have, include halogen (e.g. fluorine, chlorine,bromine, iodine, etc.), an optionally halogenated lower (C₁₋₄) alkyl, anoptionally halogenated C₁₋₄ alkoxy (e.g., methoxy, ethoxy, propoxy,butoxy, trifluoromethoxy, trifluoroethoxy, etc.), C₁₋₄ alkylenedioxy(e.g., —O—CH₂—O—, —O—CH₂—CH₂—O—, etc.), formyl, C₂₋₄ alkanoyl (e.g.,acetyl, propionyl, etc.), C₁₋₄ alkylsulfonyl (e.g., methanesulfonyl,ethanesulfonyl, etc.), phenyl-lower (C₁₋₄) alkyl, C₃₋₇ cycloalkyl,cyano, nitro, hydroxy group, an optionally substituted thiol group (e.g.thiol, C₁₋₄ alkylthio, etc.), an optionally substituted amino group(e.g. amino, mono-C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, 5- to 6-memberedcyclic amino such as tetrahydropyrrole, piperazine, piperidine,morpholine, thiomorpholine, pyrrole, imidazole, etc., etc.), anoptionally esterified or amidated carboxyl group (e.g. carboxyl, C₁₋₄alkoxy-carbonyl, carbamoyl, mono-C₁₋₄ alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, etc.), a lower (C₁₋₄) alkoxy-carbonyl, oxo group(preferably, halogen, an optionally halogenated lower (C₁₋₄) alkyl, anoptionally halogenated lower (C₁₋₄) alkoxy, phenyl-lower (C₁₋₄) alkyl,C₃₋₇ cycloalkyl, cyano, hydroxy group, etc.), etc., and the number ofthe substituents are preferably 1 to 3.

Among them, as R^(e2d), an optionally substituted acyclic hydrocarbongroup (e.g., alkyl, alkenyl, etc., each of which may be substituted) ispreferable, an optionally substituted lower C₁₋₆ alkyl group is morepreferable, and in particular, an optionally substituted methyl group ispreferable

As R^(e3d), an optionally substituted alicyclic hydrocarbon group (e.g.,cycloalkyl, cycloalkenyl, etc., each of which may be substituted;preferably, an optionally substituted lower C₃₋₈ cycloalkyl group; andmore preferably, an optionally substituted cyclohexyl) or an optionallysubstituted alicyclic heterocyclic group (preferably, an optionallysubstituted saturated alicyclic heterocyclic group (preferably, 6membered ring group)); more preferably, an optionally substitutedtetrahydropyranyl, an optionally substituted tetrahydrothiopyranyl or anoptionally substituted piperidyl; and in particular, an optionallysubstituted tetrahydropyranyl) is preferable

The compound represented by the formula (IV) may be hydrated, and thecompound represented by the formula (IV), the salt thereof and thehydrate thereof are hereinafter referred to as Compound (IV).

Compound (IV) can be produced, for example, by the following manner.

Production Method 1

As shown by the following formula, Compound (IV) can be produced byreacting a compound of the formula (IId) or a salt thereof (hereinafterreferred to as Compound (IId)) with a compound represented by theformula (IIId), a salt thereof or a reactive derivative thereof at thecarboxyl group hereinafter referred to as Compound (IIId).

(wherein each symbol has the same meaning given above)

Examples of the reactive derivative at the carboxyl group of a compoundrepresented by the formula (IIId) which can be used in an acylatingreaction include, for example, an acid halide, an acid azide, an acidanhydride, a mixed acid anhydride, an active amide, an active ester, anactive thio ester, an isocyanate, etc. Examples of the acid halideinclude, for example, an acid chloride, an acid bromide, etc.; examplesof the mixed acid anhydrides include a mono-C₁₋₆alkyl-carbonic acidmixed acid anhydride (e.g. a mixed acid anhydride of free acid andmonomethylcarbonic acid, monoethylcarbonic acid, mono-isopropylcarbonicacid, mono-isobutylcarbonic acid, mono-tert-butylcarbonic acid,mono-benzylcarbonic acid, mono-(p-nitrobenzyl)carbonic acid,mono-allylcarbonic acid, etc.), a C₁₋₆ aliphatic carboxylic acid mixedacid anhydride (e.g. a mixed acid anhydride of free acid and aceticacid, trichloroacetic acid, cyanoacetic acid, propionic acid, butyricacid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid,trifluoroacetic acid, trichloroacetic acid, acetoacetic acid, etc.), aC₇₋₁₂ aromatic carboxylic acid mixed acid anhydride (e.g. a mixed acidanhydride of free acid and benzoic acid, p-toluic acid, p-chloro benzoicacid, etc.), an organic sulfonic acid mixed acid anhydride (e.g. mixedacid anhydride of free acid and methanesulfonic acid, ethanesulfonicacid, benzenesulfonic acid, p-toluenesulfonic acid, etc.) etc.; examplesof the active amide include an amide with a nitrogen-containingheterocyclic compound (an acid amide of a free acid and, for example,pyrazole, imidazole, benzotriazole, etc., these nitrogen-containingheterocyclic compound may be substituted with a C₁₋₆alkyl group (e.g.,methyl, ethyl, etc.), a C₁₋₆alkoxy group (e.g., methoxy, ethoxy, etc.),a halogen atom (e.g., fluorine, chlorine, bromine, etc.), an oxo group,a thioxo group, a C₁₋₆alkylthio group (e.g., methylthio, ethylthio,etc.), etc.), etc.

As an active ester, all the active esters used in the field of thesynthesis of β-lactam and peptide may be used. Examples of the activeester include, for example, an organic phosphoric acid ester (e.g.diethoxyphosphoric acid ester, diphenoxyphosphoric acid ester, etc.),p-nitrophenyl ester, 2,4-dinitrophenyl ester, cyanomethyl ester,pentachlorophenyl ester, N-hydroxysuccinimide ester,N-hydroxyphthalimide ester, 1-hydroxybenzotriazole ester,6-chloro-1-hydroxybenzotriazole ester, 1-hydroxy-1H-2-pyridone ester,etc. Example's of the active thio ester include an ester of the acidwith an aromatic heterocyclic thiol compound (e.g. 2-pyridylthiol ester,2-benzothiazolylthiol ester, etc., which heterocyclics may besubstituted with a C₁₋₆alkyl group (e.g. methyl, ethyl, etc.), aC₁₋₆alkoxy group (e.g., methoxy, ethoxy, etc.), a halogen atom (e.g.,fluorine, chlorine, bromine, etc.), a C₁₋₆alkyl-thio group (e.g.,methylthio, ethylthio, etc.), etc.).

Examples of the leaving group represented by L include, for example, ahalogen atom (e.g., a chlorine atom, a bromine atom, an iodine atom,etc.), an alkyl- or aryl-sulfonyloxy group (e.g., methanesulfonyloxy,trifluoromethanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy,p-toluenesulfonyloxy, etc.), etc. The reaction is usually carried out ina solvent inert to the reaction. Examples of the use for the solventinclude an ether solvent (e.g., ethyl ether, diisoprpyl ether, dimethoxyethane, tetrahydrofuran, dioxane, etc.), a halogenated solvent (e.g.,dichloromethane, dicholoroethane, chloroform, etc.), an aromatic solvent(e.g., toluene, chlorobenzene, xylene, etc.), acetonitrile,N,N-dimethylformamide (DMF), acetone, methylethyl ketone,dimethylsulfoxide (DMSO), water, etc., or a mixed solvent thereof. Amongthem, acetonitrile, dichloromethane, chloroform, etc. are preferable.The reaction is usually carried out by using 1 to 5 equivalent,preferably 1 to 3 equivalents of Compound (IIId) relative to 1equivalent of Compound (IId). The reaction temperature ranges from −20°C. to 50° C., preferably 0° C. to room temperature, and reaction time isusually 5 minutes to 100 hours. The reaction may smoothly proceed byusing a base. As the base, an inorganic base and an organic base can beused effectively. Examples of the inorganic base include a hydroxide, ahydride, a carbonate, a bicarbonate of alkaline metal or alkaline earthmetal. Among them, potassium carbonate, sodium carbonate, sodiumhydroxide, potassium hydroxide, sodium hydrogencarbonate, potassiumhydrogencarbonate are preferable. Examples of the organic basepreferably include a tertiary amine such as triethylamine. Examples ofthe reactive derivative at the carboxyl group of the formula (IIId) areas mentioned above, and among them, an acid halide is preferable. Theused amount of the base is usually 1 to 10 equivalents, preferably 1 to3 equivalents relative to 1 equivalent of Compound (IId).

The acylation reaction in which a carboxylic acid is used is carried outin an inert solvent (e.g., a halogenated solvent, acetonitrile) byreacting one equivalent of Compound (IId) with 1 to 1.5 equivalent ofcarboxylic acid (A^(d)-CO₂H) in the presence of 1 to 1.5 equivalent ofdehydrating condensation agent such as dicyclohexyl carbodiimide (DCC),etc. The reaction is usually carried out at room temperature, and thereaction time is 0.5 to 24 hours.

Compound (IIId) used as the starting material in the reaction can beproduced by a conventional manner using a compound described inHeterocycles, 43(10) 2131-2138 (1996) etc. as a starting compound.Compound (IId) used in the method can be produced by a manner describedin Chem. Pharm. Bull. 47(1) 28-36 (1999) or Japanese unexamined patentpublication No. 53654/1981 or a similar manner thereof.

Compound (IId) wherein rd is 3 can be produced, for example, by a methoddescribed in Synthetic Comm., 1991, 20, 3167-3180.

That is, the above compound can be produced by the following method byapplying an addition reaction of amines or amides to unsaturated bond.

(wherein each symbol has the same meaning as defined above)

The compound can be produced by reacting acrolein derivatives (VId) withCompound (Vd), followed by reacting the resulting compound (VIId) withCompound (VIIId) under a condition of reduction. The reaction ofCompound (VId) with Compound (Vd) is usually carried out in a solventinert to the reaction in the presence of a base. Examples of the baseinclude 1) a strong base such as hydride of alkali metal or alkalineearth metal (e.g., lithium hydride, sodium hydride, potassium hydride,calcium hydride, etc.), an amide of an alkali metal or an alkaline earthmetal (e.g., lithium amide, sodium amide, lithium diisopropylamide,lithium dicyclohexylamide, lithium hexamethyldisilazide, sodiumhexamethyldisilazide, potassium hexamethyldisilazide, etc.), a loweralkoxide of alkali metal or alkaline earth metal (e.g., sodiummethoxide, sodium ethoxide, potassium t-butoxide, etc.), etc., 2) aninorganic base such as a hydroxide of an alkali metal or an alkalineearth metal (e.g., sodium hydroxide, potassium hydroxide, lithiumhydroxide, barium hydroxide, etc.), a carbonate of an alkali metal or analkaline earth metal (e.g., sodium carbonate, potassium carbonate,cesium carbonate, etc.), a bicarbonate of alkali metal or alkaline earthmetal (e.g., sodium hydrogencarbonate, potassium hydrogencarbonate,etc.), etc., 3) an organic base etc., such an amine as triethylamine,diisopropylethylamine, N-methylmorpholine, dimethylaminopyridine,DBU(1,8-diazabicyclo[5.4.0]-7-undecene),DBN(1,5-diazabicyclo[4.3.0]non-5-ene), etc., etc., and such basicheterocyclic Compound, etc., as pyridine, imidazole, 2,6-lutidine, etc.Examples of the solvent include those mentioned in the reaction ofCompound (IId) with Compound (IIId). These solvents can be used solelyor in combination. Compound (VIId) can be obtained in the reaction.

In the reaction between Compound (VIId) and Compound (VIIId), examplesof the reducing agent include sodium borohydride, lithium borohydride,sodium cyanoborohydride, sodium triacetoxyborohydride etc. The amount ofthe reducing agent used is usually 1 to 10 equivalents relative to 1equivalent of Compound (VIId), preferably 1 to 4 equivalent. Thereaction temperature is −20 to 50° C. preferably 0° C. to ambienttemperature, and the reaction time is 0.5 to 24 hours.

The reaction can also be carried out by a catalytic reduction reaction.

The catalytic reduction reaction is carried out in the presence of acatalytic amount of a metal catalyst such as Raney nickel, platinumoxide, metallic palladium, palladium-carbon, etc., in an inert solvent(e.g., an alcohol solvent such as methanol, ethanol, isopropanol,t-butanol, etc.), at room temperature to 100° C., under a hydrogenpressure of 1 to 100 atm for 1 to 48 hours to produce Compound (IIda).

Production 2

As shown below, Compound (IV) can be produced by reacting a compound(IVd) or its salt (herein after referred to as Compound (IVd)) with acompound (Vd) or its salt (herein after referred to as Compound (Vd)).

(wherein Ld is a leaving group, and the other symbols have the meaninggiven above).

Examples of the leaving group represented by L^(d) include, for example,a halogen atom (e.g., a chlorine atom, a bromine atom, an iodine atom,etc.), an alkyl or arylsulfonyloxy group (e.g., methanesulfonyloxy,trifluoromethanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy,p-toluenesulfonyloxy, etc.), etc.

The reaction can be carried out by a manner similar to that described inOrganic Functional Group Preparations 2nd ed., (Academic Press, Inc.).

The reaction is usually carried out in a solvent inert to the reaction.Examples of the solvent include an alcohol solvent, an ether solvent, ahalogenated solvent, an aromatic solvent, acetonitrile,N,N-dimethylformamide (DMF), acetone, methylethyl ketone,dimethylsulfoxide (DMSO), etc. These solvents can be used solely or incombination. Among them, acetonitrile, dimethylformamide, acetone,ethanol, etc., are preferable. The reaction temperature ranges usuallyfrom room temperature to 100° C., preferably from room temperature to50° C., and the reaction time is usually 0.5 to 1 day. In this reaction,a base is usually added in an amount of 1 to 3 equivalents relative to 1equivalent of Compound (IVd), but it is not essential. Examples of thebase include those mentioned in the reaction of Compound (II) withCompound (III).

Compound (IVd) used as the starting material in this reaction can beproduced by a known conventional manner with the use of Compound (IIId)as a starting material. Examples of the salt of a compound of theformulas (I) (II), (III), (IV) and (eI) of the present invention includean acid addition salt such as a salt of an inorganic acid (e.g.,hydrochloric acid salt, sulfuric acid salt, hydrobromic acid salt,phosphoric acid salt, etc.), a salt of an organic acid (e.g., aceticacid salt, trifluoroacetic acid salt, succinic acid salt, maleic acidsalt, fumaric acid salt, propionic acid salt, citric acid salt, tartaricacid salt, lactic acid salt, oxalic acid salt, methanesulfonic acidsalt, p-toluenesulfonic acid salt, etc.), etc., a salt with a base (e.g.an alkali metal salt such as potassium salt, sodium salt, lithium salt,etc., an alkaline earth metal salt such as calcium salt, magnesium salt,etc., ammonium salt, a salt with an organic base such as trimethylaminesalt, triethylamine salt, tert-butyl dimethylamine salt, dibenzylmethylamine salt, benzyl dimethylamine salt, N,N-dimethylaniline salt,pyridine salt, quinoline salt, etc.).

The compounds having a CCR antagonistic effect used in the presentinvention include not only the compounds of the formulas (I), (II),(III), (IV) and (eI) and salts thereof but also compounds shown inWO00/38680, WO00/39125, EP1013276, WO00/66558, WO00/66559, WO02/074770,etc.

The preventing agent of the present invention shows an excellentpreventing effect against HIV infection for animals, especially mammals(e.g. human, monkey, pig, dog, cat, rabbit, guinea pig, rat, mouse,etc.) and is useful for the prevention of HIV infection during bloodtransfusion or when blood products are used.

The preventing agent of the present invention is low-toxic, and whenused as drug, it can be used as it is or by mixing with pharmaceuticallyacceptable carriers, excipients or diluents in a conventional manner toprepare a pharmaceutical preparation such as powders, granules, tablets,capsules (including soft capsule and microcapsule), liquid drug,injections, suppositories, etc. The preventing agent can be safelyadministered orally or parenterally, and the preventing agent itself canbe administered by directly adding to blood for transfusion or bloodproduct.

In the present application, the parenteral administration includesadministration by subcutaneous injection, intravenous injection,intramuscular injection, intraperitoneal injection, intravenous drip,etc. An injectable preparation, for example, sterilized injectableaqueous suspension or oily suspension can be prepared by a method knownin this field with the use of a suitable dispersing agent, wetting agentor suspending agent. The modifier for the sterilized injectablepreparation may be diluents such as an aqueous solution which isnontoxic and capable of being parenterally administered, a sterilizedinjectable solution dissolved in a solvent or suspension. The carriersor solvents which can be used include water, Ringer solution, isotonicsodium chloride solution, etc. Furthermore, a solvent or a sterilizedfixed oil as a suspension can usually be used. For this purpose, anyfixed oil or any fatty acid can be used. For example, natural,synthesized or semisynthesized fatty oil or fatty acid, natural,synthesized or semisynthesized mono-, di- or tri-glyceride can be used.

Suppositories for rectal administration can be prepared by mixing thedrug and a suitable non-irritative excipient such as cocoa butter,polyethylene glycols, etc., which is a solid in ambient temperature anda liquid at the temperature in the intestinal tract, and which will meltand release the drug in the intestinal tract.

Solid preparations for oral administration include powders, granules,tablets, pills, capsules, etc. In the preparations, active ingredientcan be mixed with at least one additive, for example, saccharose,lactose, cellulose sugar, mannitol, maltitol, dextran, starchs, agar,alginates, chitins, chitosans, pectins, tragacanth chewing gums,acacias, gelatins, collagens, caseins, albumins, or synthesized orsemisynthesized polymers or glycerides. The preparations can containfurther additives, for example, inert diluent, lubricant such asmagnesium stearate, etc., preservative such as parabens, sorbic acid,etc. antioxidant such as ascorbic acid, α-tocopherol, cysteine, etc.,disintegrator, binding agent, thickener, buffer agent, sweetening agent,flavoring agent, and perfume, etc. Tablets and pills can also beprepared by enteric coating. Liquid drugs for oral administrationinclude pharmaceutically acceptable emulsion, syrup, elixir, suspension,and liquid, etc., which may include inert diluents, eg, water, commonlyused in the field.

The dosage of the preparation of the present invention can be selectedwith kind, age, weight and symptom of the patient, interval of theadministration, administration route, dosage form, etc.

The dosage for one patient depends on age, weight, general healthstatus, sex, meal, administration interval, administration method,excretion speed, the condition of the patient at the time of treatmentand other conditions. For example, when blood transfusion is carried outor blood product is used, the single dose of the present preparationwhich is orally administered to an adult human (body weight 60 kg) inorder to prevent HIV infection is about 0.02 to 50 mg/kg, preferably0.05 to 30 mg/kg, more preferably 0.1 to 10 mg/kg as a compound having aCCR antagonistic effect. The preparation is administered at the abovedose 1 to 3 times in a day.

The dosage range can be divided by the effective unit base. However, asmentioned above, taking the character and level of symptom, age, weight,general health status, sex, meal, administration interval,administration method, excretion speed and other factors intoconsideration, the dosage can be decided. The administration method ofthe preparation of the present invention can be properly selected, andthe preparation can be added directly to blood for transfusion or bloodproduct before blood transfusion or the use of blood product,respectively.

In this case, the preparation is desirably mixed with blood fortransfusion or blood product immediately to 24 hours before the use,preferably immediately to 12 hours before the use and the mostpreferably immediately to 6 hours before the use. At blood transfusionor when blood product is used, in case that the preventing agent of thepresent invention for HIV infection, is administered separately with theblood for transfusion or blood product, it is preferable to administerthe preventing agent 1 hour before the blood transfusion or bloodproduct use to the time of the blood transfusion or blood product use,and it is preferable to keep administering the preventing agent once tothree time a day for four weeks.

The present invention is hereinafter described in more detail by meansof the following Experiment and Formulation Example but are notconstrued as limitative to the present invention.

Experiment

By usingN,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)ammoniumchloride (Compound A) represented by the formula:

and compounds B to G represented by the formula: TABLE 1

R¹ R² R³ R⁴ Comp.B

H H CONH₂ Comp.C

H H SO₂Me Comp.D

H H

Comp.E

Me Cl CONH₂ Comp.F

Me Cl CONH₂ Comp.G

Me Cl Feach of which is CCR5 antagonistic drug, inhibitory effect on HIV growthagainst HIV infection was examined.[Method]

Cell MOLT-4/CCR5 cell (AIDS Res. Hum. Retrovir. 16, 935-941 (2000)) wasused.

Drug

The compound was dissolved to DMSO and properly diluted with the RPMI1640 medium including 10% FBS and 1 mg/mL G418 (GIBCO).

Virus

Ba-L strain which is a laboratory strain of R5 HIV-1 was used.

Infection

Infection operation was carried out by adding virus of 1000CCID₅₀ tocells (4×10⁶ cells/1 mL) and cultivating it for 6 hours. After theviruses unadsorbed to cells were removed by washing, the infected cellswere suspended in 2 ml of medium. To a 96 well plate were added 100 μLof the suspension of the infected cells and 100 μL of a test compound,and the mixture was cultivated at 37° C. under 5% CO₂ atmosphere for 3days. Three days after infection, the mixture was diluted to five timeswith a medium containing the test compound at the same concentration andfurther cultivated for 2 days. After cultivation, an amount of p24 insupernatant was measured with ELISA kit (ZeptoMetrix). The inhibitoryrate of infection was calculated as an amount of p24 of the drugadministration group to the amount of p24 of the control group.

[Result]

To HIV-1 infected cells was added the test compounds and the mixture wascultivated for 5 days. Each of the test compounds shows stronginhibitory effect on infection at the concentration of 1000 nmol/L (FIG.1).

Pharmaceutical Preparation 1 (Capsule)

(1) N,N-Dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclo-hepten-8-yl)carbonyl)amino)-benzyl)-N-(4-tetrahydropyranyl)- ammoniumchloride 40 mg (2) Lactose 70 mg (3) Fine crystalline cellulose  9 mg(4) Magnesium stearate  1 mg One capsule 120 mg 

(1), (2), (3) and ½ of (4) are mixed, and then granulated. To thegranules, the reminder of (4) is added, and the whole is filled into agelatin capsule.

Pharmaceutical Preparation 2 (Tablet)

(1) N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclo-heten-8-yl)carbonyl)amino)-benzyl)-N-(4-tetrahydropyranyl)- ammoniumchloride 40 mg (2) Lactose 58 mg (3) Corn starch 18 mg (4) Finecrystalline cellulose 3.5 mg  (5) Magnesium stearate 0.5 mg  One tablet120 mg 

(1), (2), (3), ⅔ of (4) and ½ of (5) are mixed and then granulated. Tothe granules, the reminders of (4) and (5) are added, followed bysubjecting the mixture to compression molding to prepare a tablet.

Pharmaceutical Preparation 3 (Injection)

In Distilled water for injection suitable for standard of pharmacopoeiaof Japan (10 ml) were dissolvedN,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)-benzyl)-N-(4-tetrahydropyranyl)ammoniumchloride (500 mg), mannitol (1000 mg) and Polysorbate 80 (100 mg), andto the solution distilled water for injection suitable for standard ofpharmacopoeia of Japan was added to make the volume to 20 ml. Thesolution was subjected to filtration under sterilization condition 0.2ml each of the solution is filled in a vial for injection understerilization condition and sealed.

INDUSTRIAL APPLICABILITY

The preventing agent of the present invention which contains a compoundhaving a CCR antagonistic effect can be used for the prevention of HIVinfection in transfusing blood or using a blood product.

1. An agent for preventing HIV infection in transfusing blood or using ablood product, which comrises a compound having a CCR antagonisticeffect.
 2. An agent as claimed in claim 1, wherein CCR is CCR5 and/orCCR2.
 3. An agent as claimed in claim 1, wherein the compound having CCRantagonistic effect isN-(3,4-dichlorophenyl)-1-(methylsulfonyl)-N-{3-[4-({4-[(methylsulfonyl)amino]phenyl}sulfonyl)-1-piperidinyl]propyl}-4-piperidinecarboxamide,N-(3-chlorophenyl)-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamide,N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,1-acetyl-N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3-chloro-4-methylphenyl)-4-piperidinecarboxamide,N-(3,4-dichlorophenyl)-N-(3-{4-[4-(ethylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,N-(3,4-dichlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,N-(3-chlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,N-(3-chlorophenyl)-N-(3-{4-[4-(ethylsulfonyl)benzyl]-1-piperidinyl}propyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamide,N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3-chloro-4-methylphenyl)-1-(methylsulfonyl)-4-piperidinecarboxamide,N-[3-(4-benzyl-1-piperidinyl)propyl]-N′-(4-chlorophenyl)-N-phenylurea,N′-(4-chlorophenyl)-N-{3-[4-(4-fluorobenzyl)-1-piperidinyl]propyl}-N-phenylurea,N′-(4-chlorophenyl)-N-(3-{4-[4-(4-morpholinylsulfonyl)benzyl]-1-piperidinyl}propyl)-N-phenylurea,N′-(4-chlorophenyl)-N-(3-{4-[4-(4-methylsulfonyl)benzyl]-1-piperidinyl}propyl)-N-phenylurea,4-{[1-(3-{[(4-chloroanilino)carbonyl]anilino}propyl)-4-piperidinyl]methyl}benzamide,N-[3-(4-benzyl-1-piperidinyl)propyl]-N-(3,4-dichlorophenyl)-1-methyl-5-oxo-3-pyrrolidinecarboxamide,1-benzyl-N-[3-(4-benzyl-1-piperidinyl)propyl]-5-oxo-N-phenyl-3-pyrrolidinecarboxamide,N-[3-(4-benzyl-1-piperidinyl)propyl]-1-(2-chlorobenzyl)-5-oxo-N-phenyl-3-pyrrolidinecarboxamide,N-(3,4-dichlorophenyl)-N-{3-[4-(4-fluorobenzyl)-1-piperidinyl]propyl}-1-methyl-5-oxo-3-pyrrolidinecarboxamide,N-[3-(4-benzyl-1-piperidinyl)propyl]-5-oxo-N-phenyl-1-(2,2,2-trifluoroethyl)-3-pyrrolidinecarboxamide,N-(3,4-dichlorophenyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-2-[1-(methylsulfonyl)-4-piperidinyl]acetamide,N-(3,4-dichlorophenyl)-N-(3-{4-[4-(isopropylsulfonyl)benzyl]-1-piperidinyl}propyl)-2-[1-(methylsulfonyl)-4-piperidinyl]acetamide,3-(1-acetyl-4-piperidinyl)-N-(3,4-dichlorophenyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)propanamide,orN-(3,4-dichlorophenyl)-4-hydroxy-1-(methylsulfonyl)-N-(3-{4-[4-(methylsulfonyl)benzyl]-1-piperidinyl}propyl)-4-piperidinecarboxamideor a salt thereof.
 4. An agent as claimed in claim 1, wherein thecompound having CCR antagonistic effect isN-methyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]piperidiniumiodide,N-methyl-N-[4-[[[7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-yl]carbonyl]amino]benzyl]piperidiniumiodide,N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-carboxamide,N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1-benzoxepin-4-carboxamide,7-(4-ethoxyphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-2,3-dihydro-1-benzoxepin-4-carboxamide,N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]-N-(tetrahydropyran-4-yl)ammoniumiodide,N-methyl-N-[4-[[[7-(4-methylphenyl)-3,4-dihydronaphthalen-2-yl]carbonyl]amino]benzyl]piperidiniumiodide,N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)ammoniumchloride,N,N-dimethyl-N-(((7-(4-methylphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N-(4-oxocyclohexyl)ammoniumchloride,N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammoniumchloride,N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-7-(4-propoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-(4-butoxyphenyl)-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[4-[N-methyl-N-(2-propoxyethyl)amino]phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[4-(2-ethoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[4-(2-ethoxyethoxy)-3,5-dimethylphenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[2-chloro-4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-(3-methyl-4-propoxyphenyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-(3,4-dipropoxyphenyl)-N-(4-((N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino)methyl)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepin-4-carboxamide,7-[4-(2-ethoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,1-ethyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-ethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-ethoxyethoxy)phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,1-formyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-1-propyl-2,3-dihydro-1-benzoazepin-4-carboxamide,N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-1-propyl-2,3-dihydro-1-benzoazepin-4-carboxamide,1-benzyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-cyclopropylmethyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-phenyl-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-(3,4-methylenedioxy)phenyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-(2-methyloxazol-5-yl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,1-allyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(3-thienyl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(thiazol-2-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-(1-methylpyrazol-4-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-(3-methylisothiazol-5-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-(1-ethylpyrazol-4-yl)methyl-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,1-isobutyl-N-[4-[[N-methyl-N-(tetrahydropyran-5-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(thiazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(1-methyltetrazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamide,or7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1-(2-methyltetrazol-5-yl)methyl-2,3-dihydro-1-benzoazepin-4-carboxamideor a salt thereof.
 5. Blood for transfusion or blood product, whichcontains a compound having a CCR antagonistic effect.
 6. A method forpreventing HIV infection which comprises administering a blood fortransfusion or blood product each of which contains a compound havingCCR antagonistic effect.
 7. A method for preventing HIV infection whichcomprises administering an effective amount of a compound having CCRantagonistic effect in transfusing blood transfusion or using a bloodproduct.
 8. A method as claimed in claim 7, wherein the time of bloodtransfusion or blood product use is from one hour before bloodtransfusion or blood product use to the time of blood transfusion orblood product use.